Collectin-11/MASP complex formation triggers activation of the lectin complement pathway--the fifth lectin pathway initiation complex

DEFF Research Database (Denmark)

Ma, Ying Jie; Skjoedt, Mikkel-Ole; Garred, Peter

2013-01-01

Collectins and ficolins are important in the clearance of endogenous and exogenous danger materials. A new human collectin-11 was recently identified in low concentration in serum in complex with mannose-binding lectin (MBL)/ficolin-associated serine proteases. Collectin-11 binds to carbohydrate...... complement complex on C. albicans. Moreover, spiking collectin-11-depleted serum, which did not mediate complement activation, with recombinant collectin-11 restored the complement activation capability. These results define collectin-11 as the fifth recognition molecule in the lectin complement pathway...

Classical Complement Pathway Activation in the Kidneys of Women With Preeclampsia.

Science.gov (United States)

Penning, Marlies; Chua, Jamie S; van Kooten, Cees; Zandbergen, Malu; Buurma, Aletta; Schutte, Joke; Bruijn, Jan Anthonie; Khankin, Eliyahu V; Bloemenkamp, Kitty; Karumanchi, S Ananth; Baelde, Hans

2015-07-01

A growing body of evidence suggests that complement dysregulation plays a role in the pathogenesis of preeclampsia. The kidney is one of the major organs affected in preeclampsia. Because the kidney is highly susceptible to complement activation, we hypothesized that preeclampsia is associated with renal complement activation. We performed a nationwide search for renal autopsy material in the Netherlands using a computerized database (PALGA). Renal tissue was obtained from 11 women with preeclampsia, 25 pregnant controls, and 14 nonpregnant controls with hypertension. The samples were immunostained for C4d, C1q, mannose-binding lectin, properdin, C3d, C5b-9, IgA, IgG, and IgM. Preeclampsia was significantly associated with renal C4d-a stable marker of complement activation-and the classical pathway marker C1q. In addition, the prevalence of IgM was significantly higher in the kidneys of the preeclamptic women. No other complement markers studied differed between the groups. Our findings in human samples were validated using a soluble fms-like tyrosine kinase 1 mouse model of preeclampsia. The kidneys in the soluble fms-like tyrosine kinase 1-injected mice had significantly more C4 deposits than the control mice. The association between preeclampsia and renal C4d, C1q, and IgM levels suggests that the classical complement pathway is involved in the renal injury in preeclampsia. Moreover, our finding that soluble fms-like tyrosine kinase 1-injected mice develop excess C4 deposits indicates that angiogenic dysregulation may play a role in complement activation within the kidney. We suggest that inhibiting complement activation may be beneficial for preventing the renal manifestations of preeclampsia. © 2015 American Heart Association, Inc.

The Emerging Role of Complement Lectin Pathway in Trypanosomatids: Molecular Bases in Activation, Genetic Deficiencies, Susceptibility to Infection, and Complement System-Based Therapeutics

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Ingrid Evans-Osses

2013-01-01

Full Text Available The innate immune system is evolutionary and ancient and is the pivotal line of the host defense system to protect against invading pathogens and abnormal self-derived components. Cellular and molecular components are involved in recognition and effector mechanisms for a successful innate immune response. The complement lectin pathway (CLP was discovered in 1990. These new components at the complement world are very efficient. Mannan-binding lectin (MBL and ficolin not only recognize many molecular patterns of pathogens rapidly to activate complement but also display several strategies to evade innate immunity. Many studies have shown a relation between the deficit of complement factors and susceptibility to infection. The recently discovered CLP was shown to be important in host defense against protozoan microbes. Although the recognition of pathogen-associated molecular patterns by MBL and Ficolins reveal efficient complement activations, an increase in deficiency of complement factors and diversity of parasite strategies of immune evasion demonstrate the unsuccessful effort to control the infection. In the present paper, we will discuss basic aspects of complement activation, the structure of the lectin pathway components, genetic deficiency of complement factors, and new therapeutic opportunities to target the complement system to control infection.

Detection of deregulated modules using deregulatory linked path.

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Yuxuan Hu

Full Text Available The identification of deregulated modules (such as induced by oncogenes is a crucial step for exploring the pathogenic process of complex diseases. Most of the existing methods focus on deregulation of genes rather than the links of the path among them. In this study, we emphasize on the detection of deregulated links, and develop a novel and effective regulatory path-based approach in finding deregulated modules. Observing that a regulatory pathway between two genes might involve in multiple rather than a single path, we identify condition-specific core regulatory path (CCRP to detect the significant deregulation of regulatory links. Using time-series gene expression, we define the regulatory strength within each gene pair based on statistical dependence analysis. The CCRPs in regulatory networks can then be identified using the shortest path algorithm. Finally, we derive the deregulated modules by integrating the differential edges (as deregulated links of the CCRPs between the case and the control group. To demonstrate the effectiveness of our approach, we apply the method to expression data associated with different states of Human Epidermal Growth Factor Receptor 2 (HER2. The experimental results show that the genes as well as the links in the deregulated modules are significantly enriched in multiple KEGG pathways and GO biological processes, most of which can be validated to suffer from impact of this oncogene based on previous studies. Additionally, we find the regulatory mechanism associated with the crucial gene SNAI1 significantly deregulated resulting from the activation of HER2. Hence, our method provides not only a strategy for detecting the deregulated links in regulatory networks, but also a way to identify concerning deregulated modules, thus contributing to the target selection of edgetic drugs.

Activation of the lectin complement pathway on human renal ...

African Journals Online (AJOL)

This study aimed to investigate the roles of high glucose and mannose-binding lectin (MBL) on the activation of the lectin complement pathway (LCP) on human renal glomerular endothelial cells (HRGECs) in vitro. Flow cytometry analysis, immunofluorescence staining and Western blot were used to detect the cell surface ...

The lectin pathway of complement activation is a critical component of the innate immune response to pneumococcal infection

DEFF Research Database (Denmark)

Ali, Youssif M; Lynch, Nicholas J; Haleem, Kashif S

2012-01-01

The complement system plays a key role in host defense against pneumococcal infection. Three different pathways, the classical, alternative and lectin pathways, mediate complement activation. While there is limited information available on the roles of the classical and the alternative activation...... to pneumococcal infection and fail to opsonize Streptococcus pneumoniae in the none-immune host. This defect in complement opsonisation severely compromises pathogen clearance in the lectin pathway deficient host. Using sera from mice and humans with defined complement deficiencies, we demonstrate that mouse...... of C4. This study corroborates the essential function of MASP-2 in the lectin pathway and highlights the importance of MBL-independent lectin pathway activation in the host defense against pneumococci....

Metabolic Disorder, Inflammation, and Deregulated Molecular Pathways Converging in Pancreatic Cancer Development: Implications for New Therapeutic Strategies

International Nuclear Information System (INIS)

Motoo, Yoshiharu; Shimasaki, Takeo; Ishigaki, Yasuhito; Nakajima, Hideo; Kawakami, Kazuyuki; Minamoto, Toshinari

2011-01-01

Pancreatic cancer develops and progresses through complex, cumulative biological processes involving metabolic disorder, local inflammation, and deregulated molecular pathways. The resulting tumor aggressiveness hampers surgical intervention and renders pancreatic cancer resistant to standard chemotherapy and radiation therapy. Based on these pathologic properties, several therapeutic strategies are being developed to reverse refractory pancreatic cancer. Here, we outline molecular targeting therapies, which are primarily directed against growth factor receptor-type tyrosine kinases deregulated in tumors, but have failed to improve the survival of pancreatic cancer patients. Glycogen synthase kinase-3β (GSK3β) is a member of a serine/threonine protein kinase family that plays a critical role in various cellular pathways. GSK3β has also emerged as a mediator of pathological states, including glucose intolerance, inflammation, and various cancers (e.g., pancreatic cancer). We review recent studies that demonstrate the anti-tumor effects of GSK3β inhibition alone or in combination with chemotherapy and radiation. GSK3β inhibition may exert indirect anti-tumor actions in pancreatic cancer by modulating metabolic disorder and inflammation

Metabolic Disorder, Inflammation, and Deregulated Molecular Pathways Converging in Pancreatic Cancer Development: Implications for New Therapeutic Strategies

Energy Technology Data Exchange (ETDEWEB)

Motoo, Yoshiharu, E-mail: motoo@kanazawa-med.ac.jp [Department of Medical Oncology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920-0293 (Japan); Shimasaki, Takeo [Department of Medical Oncology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920-0293 (Japan); Division of Translational & Clinical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa (Japan); Ishigaki, Yasuhito [Medical Research Institute, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920-0293 (Japan); Nakajima, Hideo [Department of Medical Oncology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920-0293 (Japan); Kawakami, Kazuyuki; Minamoto, Toshinari [Division of Translational & Clinical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa (Japan)

2011-01-24

Pancreatic cancer develops and progresses through complex, cumulative biological processes involving metabolic disorder, local inflammation, and deregulated molecular pathways. The resulting tumor aggressiveness hampers surgical intervention and renders pancreatic cancer resistant to standard chemotherapy and radiation therapy. Based on these pathologic properties, several therapeutic strategies are being developed to reverse refractory pancreatic cancer. Here, we outline molecular targeting therapies, which are primarily directed against growth factor receptor-type tyrosine kinases deregulated in tumors, but have failed to improve the survival of pancreatic cancer patients. Glycogen synthase kinase-3β (GSK3β) is a member of a serine/threonine protein kinase family that plays a critical role in various cellular pathways. GSK3β has also emerged as a mediator of pathological states, including glucose intolerance, inflammation, and various cancers (e.g., pancreatic cancer). We review recent studies that demonstrate the anti-tumor effects of GSK3β inhibition alone or in combination with chemotherapy and radiation. GSK3β inhibition may exert indirect anti-tumor actions in pancreatic cancer by modulating metabolic disorder and inflammation.

Metabolic Disorder, Inflammation, and Deregulated Molecular Pathways Converging in Pancreatic Cancer Development: Implications for New Therapeutic Strategies

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Toshinari Minamoto

2011-01-01

Full Text Available Pancreatic cancer develops and progresses through complex, cumulative biological processes involving metabolic disorder, local inflammation, and deregulated molecular pathways. The resulting tumor aggressiveness hampers surgical intervention and renders pancreatic cancer resistant to standard chemotherapy and radiation therapy. Based on these pathologic properties, several therapeutic strategies are being developed to reverse refractory pancreatic cancer. Here, we outline molecular targeting therapies, which are primarily directed against growth factor receptor-type tyrosine kinases deregulated in tumors, but have failed to improve the survival of pancreatic cancer patients. Glycogen synthase kinase-3β (GSK3β is a member of a serine/threonine protein kinase family that plays a critical role in various cellular pathways. GSK3β has also emerged as a mediator of pathological states, including glucose intolerance, inflammation, and various cancers (e.g., pancreatic cancer. We review recent studies that demonstrate the anti-tumor effects of GSK3β inhibition alone or in combination with chemotherapy and radiation. GSK3β inhibition may exert indirect anti-tumor actions in pancreatic cancer by modulating metabolic disorder and inflammation.

A potent complement factor C3 specific nanobody inhibiting multiple functions in the alternative pathway of human and murine complement

DEFF Research Database (Denmark)

Jensen, Rasmus K; Pihl, Rasmus; Gadeberg, Trine A F

2018-01-01

The complement system is a complex, carefully regulated proteolytic cascade for which suppression of aberrant activation is of increasing clinical relevance and inhibition of the complement alternative pathway is a subject of intense research. Here, we describe the nanobody hC3Nb1 that binds...... to multiple functional states of C3 with sub-nanomolar affinity. The nanobody causes a complete shutdown of alternative pathway activity in human and murine serum when present in concentrations comparable to C3, and hC3Nb1 is shown to prevent both proconvertase assembly as well as binding of the C3 substrate...... to C3 convertases. Our crystal structure of the C3b-hC3Nb1 complex and functional experiments demonstrate that proconvertase formation is blocked by steric hindrance between the nanobody and an Asn-linked glycan on complement factor B. In addition, hC3Nb1 is shown to prevent factor H binding to C3b...

Cholesterol Crystals Activate the Lectin Complement Pathway via Ficolin-2 and Mannose-Binding Lectin

DEFF Research Database (Denmark)

Pilely, Katrine; Rosbjerg, Anne; Genster, Ninette

2016-01-01

Cholesterol crystals (CC) play an essential role in the formation of atherosclerotic plaques. CC activate the classical and the alternative complement pathways, but the role of the lectin pathway is unknown. We hypothesized that the pattern recognition molecules (PRMs) from the lectin pathway bind...... CC and function as an upstream innate inflammatory signal in the pathophysiology of atherosclerosis. We investigated the binding of the PRMs mannose-binding lectin (MBL), ficolin-1, ficolin-2, and ficolin-3, the associated serine proteases, and complement activation products to CC in vitro using...... recognize CC and provides evidence for an important role for this pathway in the inflammatory response induced by CC in the pathophysiology of atherosclerosis....

Deregulation of Interferon Signaling in Malignant Cells

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Leonidas C. Platanias

2010-02-01

Full Text Available Interferons (IFNs are a family of cytokines with potent antiproliferative, antiviral, and immunomodulatory properties. Much has been learned about IFNs and IFN-activated signaling cascades over the last 50 years. Due to their potent antitumor effects in vitro and in vivo, recombinant IFNs have been used extensively over the years, alone or in combination with other drugs, for the treatment of various malignancies. This review summarizes the current knowledge on IFN signaling components and pathways that are deregulated in human malignancies. The relevance of deregulation of IFN signaling pathways in defective innate immune surveillance and tumorigenesis are discussed.

Mutations in the HECT domain of NEDD4L lead to AKT-mTOR pathway deregulation and cause periventricular nodular heterotopia.

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Broix, Loïc; Jagline, Hélène; Ivanova, Ekaterina; Schmucker, Stéphane; Drouot, Nathalie; Clayton-Smith, Jill; Pagnamenta, Alistair T; Metcalfe, Kay A; Isidor, Bertrand; Louvier, Ulrike Walther; Poduri, Annapurna; Taylor, Jenny C; Tilly, Peggy; Poirier, Karine; Saillour, Yoann; Lebrun, Nicolas; Stemmelen, Tristan; Rudolf, Gabrielle; Muraca, Giuseppe; Saintpierre, Benjamin; Elmorjani, Adrienne; Moïse, Martin; Weirauch, Nathalie Bednarek; Guerrini, Renzo; Boland, Anne; Olaso, Robert; Masson, Cecile; Tripathy, Ratna; Keays, David; Beldjord, Cherif; Nguyen, Laurent; Godin, Juliette; Kini, Usha; Nischké, Patrick; Deleuze, Jean-François; Bahi-Buisson, Nadia; Sumara, Izabela; Hinckelmann, Maria-Victoria; Chelly, Jamel

2016-11-01

Neurodevelopmental disorders with periventricular nodular heterotopia (PNH) are etiologically heterogeneous, and their genetic causes remain in many cases unknown. Here we show that missense mutations in NEDD4L mapping to the HECT domain of the encoded E3 ubiquitin ligase lead to PNH associated with toe syndactyly, cleft palate and neurodevelopmental delay. Cellular and expression data showed sensitivity of PNH-associated mutants to proteasome degradation. Moreover, an in utero electroporation approach showed that PNH-related mutants and excess wild-type NEDD4L affect neurogenesis, neuronal positioning and terminal translocation. Further investigations, including rapamycin-based experiments, found differential deregulation of pathways involved. Excess wild-type NEDD4L leads to disruption of Dab1 and mTORC1 pathways, while PNH-related mutations are associated with deregulation of mTORC1 and AKT activities. Altogether, these data provide insights into the critical role of NEDD4L in the regulation of mTOR pathways and their contributions in cortical development.

Tuning complement activation and pathway through controlled molecular architecture of dextran chains in nanoparticle corona.

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Coty, Jean-Baptiste; Eleamen Oliveira, Elquio; Vauthier, Christine

2017-11-05

The understanding of complement activation by nanomaterials is a key to a rational design of safe and efficient nanomedicines. This work proposed a systematic study investigating how molecular design of nanoparticle coronas made of dextran impacts on mechanisms that trigger complement activation. The nanoparticles used for this work consisted of dextran-coated poly(isobutylcyanoacrylate) (PIBCA) nanoparticles have already been thoroughly characterized. Their different capacity to trigger complement activation established on the cleavage of the protein C3 was also already described making these nanoparticles good models to investigate the relation between the molecular feature of their corona and the mechanism by which they triggered complement activation. Results of this new study show that complement activation pathways can be selected by distinct architectures formed by dextran chains composing the nanoparticle corona. Assumptions that explain the relation between complement activation mechanisms triggered by the nanoparticles and the nanoparticle corona molecular feature were proposed. These results are of interest to better understand how the design of dextran-coated nanomaterials will impact interactions with the complement system. It can open perspectives with regard to the selection of a preferential complement activation pathway or prevent the nanoparticles to activate the complement system, based on a rational choice of the corona configuration. Copyright © 2017 Elsevier B.V. All rights reserved.

An Ixodes ricinus Tick Salivary Lectin Pathway Inhibitor Protects Borrelia burgdorferi sensu lato from Human Complement.

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Wagemakers, Alex; Coumou, Jeroen; Schuijt, Tim J; Oei, Anneke; Nijhof, Ard M; van 't Veer, Cornelis; van der Poll, Tom; Bins, Adriaan D; Hovius, Joppe W R

2016-04-01

We previously identified tick salivary lectin pathway inhibitor (TSLPI) in Ixodes scapularis, a vector for Borrelia burgdorferi sensu stricto (s.s.) in North America. TSLPI is a salivary protein facilitating B. burgdorferi s.s. transmission and acquisition by inhibiting the host lectin complement pathway through interference with mannose binding lectin (MBL) activity. Since Ixodes ricinus is the predominant vector for Lyme borreliosis in Europe and transmits several complement sensitive B. burgdorferi sensu lato (s.l.) strains, we aimed to identify, describe, and characterize the I. ricinus ortholog of TSLPI. We performed (q)PCRs on I. ricinus salivary gland cDNA to identify a TSLPI ortholog. Next, we generated recombinant (r)TSLPI in a Drosophila expression system and examined inhibition of the MBL complement pathway and complement-mediated killing of B. burgdorferi s.l. in vitro. We identified a TSLPI ortholog in I. ricinus salivary glands with 93% homology at the RNA and 89% at the protein level compared to I. scapularis TSLPI, which was upregulated during tick feeding. In silico analysis revealed that TSLPI appears to be part of a larger family of Ixodes salivary proteins among which I. persulcatus basic tail salivary proteins and I. scapularis TSLPI and Salp14. I. ricinus rTSLPI inhibited the MBL complement pathway and protected B. burgdorferi s.s. and Borrelia garinii from complement-mediated killing. We have identified a TSLPI ortholog, which protects B. burgdorferi s.l. from complement-mediated killing in I. ricinus, the major vector for tick-borne diseases in Europe.

Activation of the classical pathway of complement by tobacco glycoprotein (TGP).

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Koethe, S M; Nelson, K E; Becker, C G

1995-07-15

Tobacco glycoprotein (TGP), a polyphenol-rich glycoprotein isolated from tobacco leaves, activates the classical complement pathway through a mechanism that appears to involve direct interaction with C1q. A binding site on C1q for TGP can be localized by competitive inhibition with DNA to a region located in the junction between the collagen-like and globular regions of the molecule. A protein with activity similar to TGP has also been isolated from cigarette smoke condensate (TGP-S); it shares a binding site on C1q with TGP and has similar functional activity, with the exception that complement activation does not proceed to formation of a C3 cleaving enzyme. The ability of TGP and TGP-S to activate complement can be partially duplicated using polyphenols associated with tobacco leaf and smoke, i.e., chlorogenic acid and rutin. These polyphenols also compete with TGP for a binding site on immobilized C1q, suggesting that the polyphenol portion of TGP is critical for activation of complement. These results provide an additional mechanism for complement activation by cigarette products that, in vivo, could result in a localized complement depletion, generation of biologically active complement cleavage products, and initiation of an inflammatory response.

A journey through the lectin pathway of complement-MBL and beyond

DEFF Research Database (Denmark)

Garred, Peter; Genster, Ninette; Pilely, Katrine

2016-01-01

, and Carnevale) embryonic development syndrome originates from rare mutations affecting either collectin-11 or MASP-3, indicating a broader functionality of the complement system than previously anticipated. This review summarizes the characteristics of the molecules in the lectin pathway....

Functional assay of the alternative complement pathway of rat serum

International Nuclear Information System (INIS)

Coonrod, J.D.; Jenkins, S.D.

1979-01-01

Two functional assays of the alternative pathway of complement activation in rat serum were developed. In the first assay, conditions were established for titration of alternative pathway activity by use of the 50% hemolytic end-point of rabbit red blood cells (RaRBC) in serum treated with ethyleneglycol-bis-(beta-aminoethyl ether)-N, N'-tetraacetic acid (EGTA). The second assay of alternative pathway activity was based on the opsonization of heat-killed radiolabeled pneumococci of serotype 25 (Pn25). Opsonization of Pn25 was shown to proceed entirely via the alternative pathway in rat serum. There was excellent correlation between the results obtained with the RaRBC lysis test and those obtained with the opsonization test. Because of its technical simplicity, the RaRBC lysis test appeared to be the single most useful test of alternative pathway activity in rat serum. (Auth.)

Sotos syndrome is associated with deregulation of the MAPK/ERK-signaling pathway.

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Remco Visser

Full Text Available Sotos syndrome (SoS is characterized by tall stature, characteristic craniofacial features and mental retardation. It is caused by haploinsufficiency of the NSD1 gene. In this study, our objective was to identify downstream effectors of NSD1 and to map these effectors in signaling pathways associated with growth. Genome-wide expression studies were performed on dermal fibroblasts from SoS patients with a confirmed NSD1 abnormality. To substantiate those results, phosphorylation, siRNA and transfection experiments were performed. A significant association was demonstrated with the Mitogen-Activated Protein Kinase (MAPK pathway. Members of the fibroblast growth factor family such as FGF4 and FGF13 contributed strongly to the differential expression in this pathway. In addition, a diminished activity state of the MAPK/ERK pathway was demonstrated in SoS. The Ras Interacting Protein 1 (RASIP1 was identified to exhibit upregulated expression in SoS. It was shown that RASIP1 dose-dependently potentiated bFGF induced expression of the MAPK responsive SBE reporter providing further support for a link between NSD1 and the MAPK/ERK signaling pathway. Additionally, we demonstrated NSD1 expression in the terminally differentiated hypertrophic chondrocytes of normal human epiphyseal growth plates. In short stature syndromes such as hypochondroplasia and Noonan syndrome, the activation level of the FGF-MAPK/ERK-pathway in epiphyseal growth plates is a determining factor for statural growth. In analogy, we propose that deregulation of the MAPK/ERK pathway in SoS results in altered hypertrophic differentiation of NSD1 expressing chondrocytes and may be a determining factor in statural overgrowth and accelerated skeletal maturation in SoS.

Malaria parasite evasion of classical complement pathway attack

DEFF Research Database (Denmark)

Larsen, Mads Delbo; Ditlev, Sisse; Olmos, Rafael Bayarri

2017-01-01

of the protective antibodies that are gradually acquired in response to P. falciparum-IEs. Although this response is dominated by IgG1 and IgG3, complement-mediated attack following activation of the classical pathway does not appear to be a major effector mechanism. We hypothesized that this is related to the knob...... is that the knob-restricted expression of PfEMP1 on the IE surface may serve as a hitherto unappreciated immune evasion mechanism employed by P. falciparum parasites....

The Lectin Complement Pathway in Patients with Necrotizing Soft Tissue Infection

DEFF Research Database (Denmark)

Hansen, Marco Bo; Rasmussen, Lars S; Pilely, Katrine

2016-01-01

BACKGROUND: Mannose-binding lectin (MBL) and ficolins are pattern recognition molecules (PRMs) that play an important role during infection through activation of the lectin complement pathway. We assessed whether plasma PRM levels were associated with mortality in patients with necrotizing soft t...

Depressed activation of the lectin pathway of complement in hereditary angioedema

DEFF Research Database (Denmark)

Varga, L; Széplaki, G; Laki, J

2008-01-01

) in three complement activation pathways. Functional activity of the CP, LP and AP were measured in the sera of 68 adult patients with hereditary angioedema (HAE) and 64 healthy controls. In addition, the level of C1q, MBL, MBL-associated serine protease-2 (MASP-2), C4-, C3- and C1INH was measured...... by standard laboratory methods. MBL-2 genotypes were determined by polymerase chain reaction. Besides the complement alterations (low CP and C1INH activity, low C4-, C1INH concentrations), which characterize HAE, the level of MASP-2 was also lower (P = 0.0001) in patients compared with controls. Depressed LP...

Lectin Pathway of Complement Activation Is Associated with Vulnerability of Atherosclerotic Plaques

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Fumagalli, Stefano; Perego, Carlo; Zangari, Rosalia

2017-01-01

Inflammatory mechanisms may be involved in atherosclerotic plaque rupture. By using a novel histology-based method to quantify plaque instability here, we assess whether lectin pathway (LP) of complement activation, a major inflammation arm, could represent an index of plaque instability. Plaques...

Bioactive lysophospholipids generated by hepatic lipase degradation of lipoproteins lead to complement activation via the classical pathway.

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Ma, Wanchao; Paik, David C; Barile, Gaetano R

2014-09-09

We determined bioactivity of lysophospholipids generated by degradation of the low-density (LDL), very low-density (VLDL), and high-density (HDL) lipoproteins with hepatic lipase (HL), cholesterol esterase (CE), and lipoprotein-associated phospholipase A2 (Lp-PLA2). The LDL, VLDL, and HDL were treated with HL, CE, and Lp-PLA2 after immobilization on plates, and complement activation studies were performed with diluted human serum. Complement component 3 (C3) fixation, a marker for complement activation, was determined with a monoclonal anti-human C3d antibody. Enzymatic properties of HL and CE were assayed with triglyceride and phosphatidylcholine substrates for triglyceride hydrolase and phospholipase A activities. The ARPE-19 cells were used for viability studies. The HL degradation of human lipoproteins LDL, VLDL, or HDL results in the formation of modified lipoproteins that can activate the complement pathway. Complement activation is dose- and time-dependent upon HL and occurs via the classical pathway. Enzymatic studies suggest that the phospholipase A1 activity of HL generates complement-activating lysophospholipids. C-reactive protein (CRP), known to simultaneously interact with complement C1 and complement factor H (CFH), further enhances HL-induced complement activation. The lysophospholipids, 1-Palmitoyl-sn-glycero-3-phosphocholine and 1-Oleoyl-sn-glycero-3-phosphocholine, can be directly cytotoxic to ARPE-19 cells. The HL degradation of lipoproteins, known to accumulate in the outer retina and in drusen, can lead to the formation of bioactive lysophospholipids that can trigger complement activation and induce RPE cellular dysfunction. Given the known risk associations for age-related macular degeneration (AMD) with HL, CRP, and CFH, this study elucidates a possible damage pathway for age-related macular degeneration (AMD) in genetically predisposed individuals, that HL activity may lead to accumulation of lysophospholipids to initiate complement

HTLV Deregulation of the NF-κB Pathway: An Update on Tax and Antisense Proteins Role

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Fochi, Stefania; Mutascio, Simona; Bertazzoni, Umberto; Zipeto, Donato; Romanelli, Maria G.

2018-01-01

Human T-cell lymphotropic virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia (ATL), an aggressive CD4+/CD25+ T-cell malignancy and of a severe neurodegenerative disease, HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). The chronic activation or deregulation of the canonical and non-canonical nuclear factor kappa B (NF-κB) pathways play a crucial role in tumorigenesis. The HTLV-1 Tax-1 oncoprotein is a potent activator of the NF-κB transcription factors and the NF-κB response is required for promoting the development of HTLV-1 transformed cell lines. The homologous retrovirus HTLV-2, which also expresses a Tax-2 transforming protein, is not associated with ATL. In this review, we provide an updated synopsis of the role of Tax-1 in the deregulation of the NF-κB pathway, highlighting the differences with the homologous Tax-2. Special emphasis is directed toward the understanding of the molecular mechanisms involved in NF-κB activation resulting from Tax interaction with host factors affecting several cellular processes, such as cell cycle, apoptosis, senescence, cell proliferation, autophagy, and post-translational modifications. We also discuss the current knowledge on the role of the antisense viral protein HBZ in down-regulating the NF-κB activation induced by Tax, and its implication in cellular senescence. In addition, we review the recent studies on the mechanism of HBZ-mediated inhibition of NF-κB activity as compared to that exerted by the HTLV-2 antisense protein, APH-2. Finally, we discuss recent advances aimed at understanding the role exerted in the development of ATL by the perturbation of NF-κB pathway by viral regulatory proteins. PMID:29515558

HTLV Deregulation of the NF-κB Pathway: An Update on Tax and Antisense Proteins Role.

Science.gov (United States)

Fochi, Stefania; Mutascio, Simona; Bertazzoni, Umberto; Zipeto, Donato; Romanelli, Maria G

2018-01-01

Human T-cell lymphotropic virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia (ATL), an aggressive CD4 + /CD25 + T-cell malignancy and of a severe neurodegenerative disease, HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). The chronic activation or deregulation of the canonical and non-canonical nuclear factor kappa B (NF-κB) pathways play a crucial role in tumorigenesis. The HTLV-1 Tax-1 oncoprotein is a potent activator of the NF-κB transcription factors and the NF-κB response is required for promoting the development of HTLV-1 transformed cell lines. The homologous retrovirus HTLV-2, which also expresses a Tax-2 transforming protein, is not associated with ATL. In this review, we provide an updated synopsis of the role of Tax-1 in the deregulation of the NF-κB pathway, highlighting the differences with the homologous Tax-2. Special emphasis is directed toward the understanding of the molecular mechanisms involved in NF-κB activation resulting from Tax interaction with host factors affecting several cellular processes, such as cell cycle, apoptosis, senescence, cell proliferation, autophagy, and post-translational modifications. We also discuss the current knowledge on the role of the antisense viral protein HBZ in down-regulating the NF-κB activation induced by Tax, and its implication in cellular senescence. In addition, we review the recent studies on the mechanism of HBZ-mediated inhibition of NF-κB activity as compared to that exerted by the HTLV-2 antisense protein, APH-2. Finally, we discuss recent advances aimed at understanding the role exerted in the development of ATL by the perturbation of NF-κB pathway by viral regulatory proteins.

The down-stream effects of mannan-induced lectin complement pathway activation depend quantitatively on alternative pathway amplification

DEFF Research Database (Denmark)

Harboe, Morten; Garred, Peter; Karlstrøm, Ellen

2009-01-01

Complement activation plays an important role in human pathophysiology. The effect of classical pathway activation is largely dependent on alternative pathway (AP) amplification, whereas the role of AP for the down-stream effect of mannan-induced lectin pathway (LP) activation is poorly understood...... that AP amplification is quantitatively responsible for the final effect of initial specific LP activation. TCC generation on the solid phase was distinctly but less inhibited by anti-fD. C2 bypass of the LP pathway could be demonstrated, and AP amplification was also essential during C2 bypass in LP...... as shown by complete inhibition of TCC generation in C2-deficient serum by anti-fD and anti-properdin antibodies. In conclusion, the down-stream effect of LP activation depends strongly on AP amplification in normal human serum and in the C2 bypass pathway....

Inhibition of the classical pathway of the complement system by saliva of Amblyomma cajennense (Acari: Ixodidae).

Science.gov (United States)

Franco, Paula F; Silva, Naylene C S; Fazito do Vale, Vladimir; Abreu, Jéssica F; Santos, Vânia C; Gontijo, Nelder F; Valenzuela, Jesus G; Pereira, Marcos H; Sant'Anna, Mauricio R V; Gomes, Alessandra P S; Araujo, Ricardo N

2016-05-01

Inhibition of the complement system during and after haematophagy is of utmost importance for tick success in feeding and tick development. The role of such inhibition is to minimise damage to the intestinal epithelium as well as avoiding inflammation and opsonisation of salivary molecules at the bite site. Despite its importance, the salivary anti-complement activity has been characterised only in species belonging to the Ixodes ricinus complex which saliva is able to inhibit the alternative and lectin pathways. Little is known about this activity in other species of the Ixodidae family. Thus, the aim of this study was to describe the inhibition of the classical pathway of the complement system by the saliva of Amblyomma cajennense at different stages of the haematophagy. The A. cajennense saliva and salivary gland extract (SGE) were able to inhibit the complement classical pathway through haemolytic assays with higher activity observed when saliva was used. The anti-complement activity is present in the salivary glands of starving females and also in females throughout the whole feeding process, with significant higher activity soon after tick detachment. The SGE activity from both females fed on mice or horses had no significant correlation (p > 0.05) with tick body weight. The pH found in the intestinal lumen of A. cajennense was 8.04 ± 0.08 and haemolytic assays performed at pH 8.0 showed activation of the classical pathway similarly to what occurs at pH 7.4. Consequently, inhibition could be necessary to protect the tick enterocytes. Indeed, the inhibition observed by SGE was higher in pH 8.0 in comparison to pH 7.4 reinforcing the role of saliva in protecting the intestinal cells. Further studies should be carried out in order to identify the inhibitor molecule and characterise its inhibition mechanism. Copyright © 2016 Elsevier Inc. All rights reserved.

Ficolins and the lectin pathway of complement in patients with systemic lupus erythematosus

DEFF Research Database (Denmark)

Hein, Estrid; Nielsen, Louise Aas; Nielsen, Christoffer T

2015-01-01

The complement system plays a pathophysiological role in systemic lupus erythematosus (SLE). This study aims to investigate whether an association exists between the ficolins that are part of the lectin complement pathway and SLE. EDTA plasma samples from 68 Danish SLE patients and 29 healthy...... Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index] (SDI) (Rho=0.27, P=0.026). The Ficolin-1 concentration was also associated with the occurrence of arterial (P=0.0053) but not venous thrombosis (P=0.42). Finally, deposition of C4, C3 and TCC...

Targeting deregulated AMPK/mTORC1 pathways improves muscle function in myotonic dystrophy type I.

Science.gov (United States)

Brockhoff, Marielle; Rion, Nathalie; Chojnowska, Kathrin; Wiktorowicz, Tatiana; Eickhorst, Christopher; Erne, Beat; Frank, Stephan; Angelini, Corrado; Furling, Denis; Rüegg, Markus A; Sinnreich, Michael; Castets, Perrine

2017-02-01

Myotonic dystrophy type I (DM1) is a disabling multisystemic disease that predominantly affects skeletal muscle. It is caused by expanded CTG repeats in the 3'-UTR of the dystrophia myotonica protein kinase (DMPK) gene. RNA hairpins formed by elongated DMPK transcripts sequester RNA-binding proteins, leading to mis-splicing of numerous pre-mRNAs. Here, we have investigated whether DM1-associated muscle pathology is related to deregulation of central metabolic pathways, which may identify potential therapeutic targets for the disease. In a well-characterized mouse model for DM1 (HSALR mice), activation of AMPK signaling in muscle was impaired under starved conditions, while mTORC1 signaling remained active. In parallel, autophagic flux was perturbed in HSALR muscle and in cultured human DM1 myotubes. Pharmacological approaches targeting AMPK/mTORC1 signaling greatly ameliorated muscle function in HSALR mice. AICAR, an AMPK activator, led to a strong reduction of myotonia, which was accompanied by partial correction of misregulated alternative splicing. Rapamycin, an mTORC1 inhibitor, improved muscle relaxation and increased muscle force in HSALR mice without affecting splicing. These findings highlight the involvement of AMPK/mTORC1 deregulation in DM1 muscle pathophysiology and may open potential avenues for the treatment of this disease.

Complement Evasion by Pathogenic Leptospira.

Science.gov (United States)

Fraga, Tatiana Rodrigues; Isaac, Lourdes; Barbosa, Angela Silva

2016-01-01

Leptospirosis is a neglected infectious disease caused by spirochetes from the genus Leptospira . Pathogenic microorganisms, notably those which reach the blood circulation such as Leptospira , have evolved multiple strategies to escape the host complement system, which is important for innate and acquired immunity. Leptospira avoid complement-mediated killing through: (i) recruitment of host complement regulators; (ii) acquisition of host proteases that cleave complement proteins on the bacterial surface; and, (iii) secretion of proteases that inactivate complement proteins in the Leptospira surroundings. The recruitment of host soluble complement regulatory proteins includes the acquisition of Factor H (FH) and FH-like-1 (alternative pathway), C4b-binding protein (C4BP) (classical and lectin pathways), and vitronectin (Vn) (terminal pathway). Once bound to the leptospiral surface, FH and C4BP retain cofactor activity of Factor I in the cleavage of C3b and C4b, respectively. Vn acquisition by leptospires may result in terminal pathway inhibition by blocking C9 polymerization. The second evasion mechanism lies in plasminogen (PLG) binding to the leptospiral surface. In the presence of host activators, PLG is converted to enzymatically active plasmin, which is able to degrade C3b, C4b, and C5 at the surface of the pathogen. A third strategy used by leptospires to escape from complement system is the active secretion of proteases. Pathogenic, but not saprophytic leptospires, are able to secrete metalloproteases that cleave C3 (central complement molecule), Factor B (alternative pathway), and C4 and C2 (classical and lectin pathways). The purpose of this review is to fully explore these complement evasion mechanisms, which act together to favor Leptospira survival and multiplication in the host.

Increased activity of the mannan-binding lectin complement activation pathway in patients with colorectal cancer

DEFF Research Database (Denmark)

Ytting, H; Jensenius, Jens Christian; Christensen, I J

2004-01-01

BACKGROUND: Postoperative bacterial infectious complications are frequent in patients with colorectal cancer (CRC), with subsequent increased recurrence rates and poor prognosis. Deficiency of the mannan-binding lectin (MBL) complement activation pathway may cause increased risk of infection......: Serum MBL concentrations and MBL/MASP activity were determined using immunofluorometric assays. The levels are presented as the median, inter-quartile range and range. RESULTS: Serum MBL levels were significantly (P cancer (1384 (400-2188) ng/mL) (median...... in the colon or rectum, and disease stages according to Dukes' classification. No statistical difference (P=0.20) in frequency of MBL deficiency was found between the patients (20%) and the donors (27%). CONCLUSIONS: Overall, the MBL complement activation pathway is significantly increased in patients...

Dynamic Testing of Signal Transduction Deregulation During Breast Cancer Initiation

Science.gov (United States)

2012-07-01

Std. Z39.18 Victoria Seewaldt, M.D. Dynamic Testing of Signal Transduction Deregulation During Breast Cancer Initiation Duke University Durham...attomole- zeptomole range. Internal dilution curves insure a high-dynamic calibration range. DU -26 8L DU -26 6L DU -29 5R DU -22 9.2 L DU...3: Nanobiosensor technology is translated to test for pathway deregulation in RPFNA cytology obtained from 10 high-risk women with cytological

Study of the optimal reaction conditions for assay of the mouse alternative complement pathway

NARCIS (Netherlands)

Dijk, H. van; Rademaker, P.M.; Klerx, J.P.A.M.; Willers, J.M.M.

1985-01-01

The optimal reaction conditions for hemolytic assay of alternative complement pathway activity in mouse serum were investigated. A microtiter system was used, in which a number of 7.5×106 rabbit erythrocytes per test well appeared to be optimal. Rabbit erythrocytes were superior as target cells over

A zebrafish model for uremic toxicity: role of the complement pathway.

Science.gov (United States)

Berman, Nathaniel; Lectura, Melisa; Thurman, Josh; Reinecke, James; Raff, Amanda C; Melamed, Michal L; Reinecke, James; Quan, Zhe; Evans, Todd; Meyer, Timothy W; Hostetter, Thomas H

2013-01-01

Many organic solutes accumulate in end-stage renal disease (ESRD) and some are poorly removed with urea-based prescriptions for hemodialysis. However, their toxicities have been difficult to assess. We have employed an animal model, the zebrafish embryo, to test the toxicity of uremic serum compared to control. Serum was obtained from stable ESRD patients predialysis or from normal subjects. Zebrafish embryos 24 h postfertilization were exposed to experimental media at a water:human serum ratio of 3:1. Those exposed to serum from uremic subjects had significantly reduced survival at 8 h (19 ± 18 vs. 94 ± 6%, p 50 kDa, respectively). Heating serum abrogated its toxicity. EDTA, a potent inhibitor of complement by virtue of calcium chelation, reduced the toxicity of uremic serum compared to untreated uremic serum (96 ± 5 vs. 28 ± 20% survival, p < 0.016, chelated vs. nonchelated serum, respectively). Anti-factor B, a specific inhibitor of the alternative complement pathway, reduced the toxicity of uremic serum, compared to untreated uremic serum (98 ± 6 vs. 3 ± 9% survival, p < 0.016, anti-factor B treated vs. nontreated, respectively). Uremic serum is thus more toxic to zebrafish embryos than normal serum. Furthermore, this toxicity is associated with a fraction of large size, is inactivated by heat, and is reduced by both specific and nonspecific inhibitors of complement activation. Together these data lend support to the hypothesis that at least some uremic toxicities may be mediated by complement. Copyright © 2013 S. Karger AG, Basel.

Deregulation of brain insulin signaling in Alzheimer's disease.

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Chen, Yanxing; Deng, Yanqiu; Zhang, Baorong; Gong, Cheng-Xin

2014-04-01

Contrary to the previous belief that insulin does not act in the brain, studies in the last three decades have demonstrated important roles of insulin and insulin signal transduction in various functions of the central nervous system. Deregulated brain insulin signaling and its role in molecular pathogenesis have recently been reported in Alzheimer's disease (AD). In this article, we review the roles of brain insulin signaling in memory and cognition, the metabolism of amyloid β precursor protein, and tau phosphorylation. We further discuss deficiencies of brain insulin signaling and glucose metabolism, their roles in the development of AD, and recent studies that target the brain insulin signaling pathway for the treatment of AD. It is clear now that deregulation of brain insulin signaling plays an important role in the development of sporadic AD. The brain insulin signaling pathway also offers a promising therapeutic target for treating AD and probably other neurodegenerative disorders.

Genetic Association of the Porcine C9 Complement Component with Hemolytic Complement Activity

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D. V. A. Khoa

2015-09-01

Full Text Available The complement system is a part of the natural immune regulation mechanism against invading pathogens. Complement activation from three different pathways (classical, lectin, and alternative leads to the formation of C5-convertase, an enzyme for cleavage of C5 into C5a and C5b, followed by C6, C7, C8, and C9 in membrane attack complex. The C9 is the last complement component of the terminal lytic pathway, which plays an important role in lysis of the target cells depending on its self-polymerization to form transmembrane channels. To address the association of C9 with traits related to disease resistance, the complete porcine C9 cDNA was comparatively sequenced to detect single nucleotide polymorphisms (SNPs in pigs of the breeds Hampshire (HS, Duroc (DU, Berlin miniature pig (BMP, German Landrace (LR, Pietrain (PIE, and Muong Khuong (Vietnamese potbelly pig. Genotyping was performed in 417 F2 animals of a resource population (DUMI: DU×BMP that were vaccinated with Mycoplasma hyopneumoniae, Aujeszky diseases virus and porcine respiratory and reproductive syndrome virus at 6, 14 and 16 weeks of age, respectively. Two SNPs were detected within the third exon. One of them has an amino acid substitution. The European porcine breeds (LR and PIE show higher allele frequency of these SNPs than Vietnamese porcine breed (MK. Association of the substitution SNP with hemolytic complement activity indicated statistically significant differences between genotypes in the classical pathway but not in the alternative pathway. The interactions between eight time points of measurement of complement activity before and after vaccinations and genotypes were significantly different. The difference in hemolytic complement activity in the both pathways depends on genotype, kind of vaccine, age and the interaction to the other complement components. These results promote the porcine C9 (pC9 as a candidate gene to improve general animal health in the future.

Maternal and fetal alternative complement pathway activation in early severe preeclampsia.

Science.gov (United States)

Hoffman, M Camille; Rumer, Kristen K; Kramer, Anita; Lynch, Anne M; Winn, Virginia D

2014-01-01

We sought to determine whether alternative complement activation fragment Bb (Bb) levels are elevated in the maternal, fetal, and placental blood in cases of severe preeclampsia (PE) compared with normotensive controls. This was a cross-sectional study of women admitted at ≥24 weeks gestation with or without severe PE. Maternal plasma was collected at the time of enrollment. Umbilical venous cord and intervillous space blood were collected at delivery. Plasma Bb levels were assessed using ELISA. Bb levels were compared between cases and controls. Median Bb levels were higher in the maternal plasma of severe PE subjects (n = 24) than in controls (n = 20), 1.45 ± 1.03 versus 0.65 ± 0.23 μg/mL, P < 0.001. In umbilical venous plasma, Bb levels were higher in severe PE subjects (n = 15) compared with controls (n = 15), 2.48 ± 1.40 versus 1.01 ± 0.57 μg/mL, P = 0.01. Activation fragment Bb is increased in the maternal and umbilical venous blood of cases of severe PE when compared with normotensive controls. These data provide support for alternative complement pathway involvement in the pathogenesis of severe PE and demonstrate that alternative complement activation occurs not only in the maternal but also in the fetal compartment. © 2013 John Wiley & Sons Ltd.

Complement pathways and meningococcal disease : diagnostic aspects

DEFF Research Database (Denmark)

Sjöholm, A G; Truedsson, L; Jensenius, Jens Christian

2001-01-01

Complement is an immunological effector system that bridges innate and acquired immunity in several ways. There is a striking association between susceptibility to meningococcal disease and various forms of complement deficiency (1,2). In defense against bacterial infection, the most important fu...

CR2-mediated activation of the complement alternative pathway results in formation of membrane attack complexes on human B lymphocytes

DEFF Research Database (Denmark)

Nielsen, C H; Marquart, H V; Prodinger, W M

2001-01-01

the alternative pathway. Blockade of the CR2 ligand-binding site with the monoclonal antibody FE8 resulted in 56 +/- 13% and 71 +/- 9% inhibition of the C3-fragment and MAC deposition, respectively, whereas the monoclonal antibody HB135, directed against an irrelevant CR2 epitope, had no effect. Blockade......Normal human B lymphocytes activate the alternative pathway of complement via complement receptor type 2 (CR2, CD21), that binds hydrolysed C3 (iC3) and thereby promotes the formation of a membrane-bound C3 convertase. We have investigated whether this might lead to the generation of a C5...... processes on CR2, indicate that MAC formation is a consequence of alternative pathway activation....

An Ixodes ricinus Tick Salivary Lectin Pathway Inhibitor Protects Borrelia burgdorferi sensu lato from Human Complement

NARCIS (Netherlands)

Wagemakers, Alex; Coumou, Jeroen; Schuijt, Tim J.; Oei, Anneke; Nijhof, Ard M.; van 't Veer, Cornelis; van der Poll, Tom; Bins, Adriaan D.; Hovius, Joppe W. R.

2016-01-01

We previously identified tick salivary lectin pathway inhibitor (TSLPI) in Ixodes scapularis, a vector for Borrelia burgdorferi sensu stricto (s.s.) in North America. TSLPI is a salivary protein facilitating B. burgdorferi s.s. transmission and acquisition by inhibiting the host lectin complement

Modulation of post-stroke degenerative and regenerative processes and subacute protection by site-targeted inhibition of the alternative pathway of complement.

Science.gov (United States)

Alawieh, Ali; Elvington, Andrew; Zhu, Hong; Yu, Jin; Kindy, Mark S; Atkinson, Carl; Tomlinson, Stephen

2015-12-30

Complement promotes neuroinflammation and injury in models of stroke. However, complement is also being increasingly implicated in repair and regeneration after central nervous system (CNS) injury, and some complement deficiencies have been shown to provide acute, but not subacute, protection after murine stroke. Here, we investigate the dual role of complement in injury and repair after cerebral ischemia and reperfusion. We used complement-deficient mice and different complement inhibitors in a model of transient middle cerebral artery occlusion to investigate complement-dependent cellular and molecular changes that occur through the subacute phase after stroke. C3 deficiency and site-targeted complement inhibition with either CR2-Crry (inhibits all pathways) or CR2-fH (inhibits alternative pathway) significantly reduced infarct size, reduced apoptotic cell death, and improved neurological deficit score in the acute phase after stroke. However, only in CR2-fH-treated mice was there sustained protection with no evolution of injury in the subacute phase. Whereas both inhibitors significantly reduced microglia/macrophage activation and astrogliosis in the subacute phase, only CR2-fH improved neurological deficit and locomotor function, maintained neurogenesis markers, enhanced neuronal migration, and increased VEGF expression. These findings in CR2-fH-treated mice correlated with improved performance in spatial learning and passive avoidance tasks. The complement anaphylatoxins have been implicated in repair and regenerative mechanisms after CNS injury, and in this context CR2-fH significantly reduced, but did not eliminate the generation of C5a within the brain, unlike CR2-Crry that completely blocked C5a generation. Gene expression profiling revealed that CR2-fH treatment downregulated genes associated with apoptosis, TGFβ signaling, and neutrophil activation, and decreased neutrophil infiltration was confirmed by immunohistochemistry. CR2-fH upregulated genes for

Costs of electricity deregulation

International Nuclear Information System (INIS)

Woo, C.K.; King, M.

2006-01-01

The last decade has witnessed efforts throughout the world to deregulate the electricity industry, with varied results. While there have been a few qualified success stories, many challenges of deregulation have come to light. These challenges can lead to negative, even disastrous, outcomes. Based on a comprehensive literature review, this paper catalogues problems experienced in various deregulation efforts, and considers the application of the lessons learned from this history to Israel, which is considering deregulation. Failings of deregulation are found to center around the following problems: high set-up cost; complicated market design; inevitable spot price volatility; market power abuse; inefficient investment; difficulty in reducing generation cost; dysfunctional input markets; stranded cost; unequal distribution of benefits. We find that many of these problems are exacerbated by the particular circumstances faced by Israel, and advise any country or region considering deregulation to carefully consider these obstacles to success. (author)

Peptide Inhibitor of Complement C1 (PIC1 Rapidly Inhibits Complement Activation after Intravascular Injection in Rats.

Directory of Open Access Journals (Sweden)

Julia A Sharp

Full Text Available The complement system has been increasingly recognized to play a pivotal role in a variety of inflammatory and autoimmune diseases. Consequently, therapeutic modulators of the classical, lectin and alternative pathways of the complement system are currently in pre-clinical and clinical development. Our laboratory has identified a peptide that specifically inhibits the classical and lectin pathways of complement and is referred to as Peptide Inhibitor of Complement C1 (PIC1. In this study, we determined that the lead PIC1 variant demonstrates a salt-dependent binding to C1q, the initiator molecule of the classical pathway. Additionally, this peptide bound to the lectin pathway initiator molecule MBL as well as the ficolins H, M and L, suggesting a common mechanism of PIC1 inhibitory activity occurs via binding to the collagen-like tails of these collectin molecules. We further analyzed the effect of arginine and glutamic acid residue substitution on the complement inhibitory activity of our lead derivative in a hemolytic assay and found that the original sequence demonstrated superior inhibitory activity. To improve upon the solubility of the lead derivative, a pegylated, water soluble variant was developed, structurally characterized and demonstrated to inhibit complement activation in mouse plasma, as well as rat, non-human primate and human serum in vitro. After intravenous injection in rats, the pegylated derivative inhibited complement activation in the blood by 90% after 30 seconds, demonstrating extremely rapid function. Additionally, no adverse toxicological effects were observed in limited testing. Together these results show that PIC1 rapidly inhibits classical complement activation in vitro and in vivo and is functional for a variety of animal species, suggesting its utility in animal models of classical complement-mediated diseases.

Material properties in complement activation

DEFF Research Database (Denmark)

Moghimi, S. Moein; Andersen, Alina Joukainen; Ahmadvand, Davoud

2011-01-01

activation differently and through different sensing molecules and initiation pathways. The importance of material properties in triggering complement is considered and mechanistic aspects discussed. Mechanistic understanding of complement events could provide rational approaches for improved material design...

Complement-mediated solubilization of immune complexes and their interaction with complement C3 receptors

DEFF Research Database (Denmark)

Petersen, Ivan; Baatrup, Gunnar; Jepsen, H H

1985-01-01

Some of the molecular events in the complement (C)-mediated solubilization of immune complexes (IC) have been clarified in recent years. The solubilization is primarily mediated by alternative C pathway proteins whereas factors in the classical pathway accelerate the process. Components of the me......Some of the molecular events in the complement (C)-mediated solubilization of immune complexes (IC) have been clarified in recent years. The solubilization is primarily mediated by alternative C pathway proteins whereas factors in the classical pathway accelerate the process. Components...... of the cellular localization, expression and structure of the C3 receptors, especially the C3b (CR1) receptor, has been considerably extended in the last few years, whereas our understanding of the physiological role of these receptors is still fragmentary. However, it is becoming increasingly evident...

Electricity deregulation roundup : Ontario prepares for electricity deregulation and anxiously watches impact elsewhere

International Nuclear Information System (INIS)

Hurst, R.

2000-01-01

As the time for deregulation of Ontario's electric power industry approaches, consumers are watching other Canadian and American jurisdictions to see what deregulation will mean in terms of energy costs. Albertans have expressed serious concerns about the impact of deregulating their electric power industry. They found that in the four years since deregulation in their province, electricity prices increased when markets opened to competition. The proposed start date for deregulation in Ontario is November 1, 2000. This paper suggests that if investors don't put out significant resources, problems such as power shortages and brownouts could occur, as was the case in Alberta. Potential investors in the Ontario electricity market are already sceptical because the Ontario government, in an effort to protect consumers from unreasonable price increases, has tabled legislation that restricts the efforts of municipal utility companies to raise distribution rates. One step that will inspire some confidence is the recently finalized deal between Ontario Power Generation and British Energy to operate the Bruce Nuclear Power Station. Independent consultants have warned that electricity prices will continue to increase with deregulation for a least the next few years. Industrial customers will be the hardest hit. In California, America's first deregulated electricity market, the power grid is strained and prices have doubled or tripled in one year

CR2-mediated activation of the complement alternative pathway results in formation of membrane attack complexes on human B lymphocytes

DEFF Research Database (Denmark)

Nielsen, C H; Marquart, H V; Prodinger, W M

2001-01-01

of the CR1 binding site with the monoclonal antibody 3D9 also resulted in a minor reduction in MAC deposition, while FE8 and 3D9, in combination, markedly reduced deposition of both C3 fragments (91 +/- 5%) and C9 (95 +/- 3%). The kinetics of C3-fragment and MAC deposition, as well as the dependence of both......Normal human B lymphocytes activate the alternative pathway of complement via complement receptor type 2 (CR2, CD21), that binds hydrolysed C3 (iC3) and thereby promotes the formation of a membrane-bound C3 convertase. We have investigated whether this might lead to the generation of a C5...... convertase and consequent formation of membrane attack complexes (MAC). Deposition of C3 fragments and MAC was assessed on human peripheral B lymphocytes in the presence of 30% autologous serum containing 4.4 mM MgCl2/20 mM EGTA, which abrogates the classical pathway of complement without affecting...

Multiple activities of LigB potentiate virulence of Leptospira interrogans: inhibition of alternative and classical pathways of complement.

Directory of Open Access Journals (Sweden)

Henry A Choy

Full Text Available Microbial pathogens acquire the immediate imperative to avoid or counteract the formidable defense of innate immunity as soon as they overcome the initial physical barriers of the host. Many have adopted the strategy of directly disrupting the complement system through the capture of its components, using proteins on the pathogen's surface. In leptospirosis, pathogenic Leptospira spp. are resistant to complement-mediated killing, in contrast to the highly vulnerable non-pathogenic strains. Pathogenic L. interrogans uses LenA/LfhA and LcpA to respectively sequester and commandeer the function of two regulators, factor H and C4BP, which in turn bind C3b or C4b to interrupt the alternative or classical pathways of complement activation. LigB, another surface-proximal protein originally characterized as an adhesin binding multiple host proteins, has other activities suggesting its importance early in infection, including binding extracellular matrix, plasma, and cutaneous repair proteins and inhibiting hemostasis. In this study, we used a recent model of ectopic expression of LigB in the saprophyte, L. biflexa, to test the hypothesis that LigB also interacts with complement proteins C3b and C4b to promote the virulence of L. interrogans. The surface expression of LigB partially rescued the non-pathogen from killing by 5% normal human serum, showing 1.3- to 48-fold greater survival 4 to 6 d following exposure to complement than cultures of the non-expressing parental strain. Recombinant LigB7'-12 comprising the LigB-specific immunoglobulin repeats binds directly to human complement proteins, C3b and C4b, with respective K(ds of 43±26 nM and 69±18 nM. Repeats 9 to 11, previously shown to contain the binding domain for fibronectin and fibrinogen, are also important in LigB-complement interactions, which interfere with the alternative and classical pathways measured by complement-mediated hemolysis of erythrocytes. Thus, LigB is an adaptable interface

Airline Deregulation and Public Policy

Science.gov (United States)

Morrison, Steven A.; Winston, Clifford

1989-08-01

An assessment of the effects of airline deregulation on travelers and carriers indicates that deregulation has provided travelers and carriers with 14.9 billion of annual benefits (1988 dollars). Airport congestion, airline safety, airline bankruptcy, and mergers are also analyzed and found in most cases to have reduced benefits. But, these costs should not be attributed to deregulation per se, but to failures by the government to pursue appropriate policies in these areas. Pursuit of policies that promote airline competition and efficient use of airport capacity would significantly increase the benefits from deregulation and would provide valuable guidance for other industries undergoing the transition to deregulation.

AMD and the alternative complement pathway: genetics and functional implications.

Science.gov (United States)

Tan, Perciliz L; Bowes Rickman, Catherine; Katsanis, Nicholas

2016-06-21

Age-related macular degeneration (AMD) is an ocular neurodegenerative disorder and is the leading cause of legal blindness in Western societies, with a prevalence of up to 8 % over the age of 60, which continues to increase with age. AMD is characterized by the progressive breakdown of the macula (the central region of the retina), resulting in the loss of central vision including visual acuity. While its molecular etiology remains unclear, advances in genetics and genomics have illuminated the genetic architecture of the disease and have generated attractive pathomechanistic hypotheses. Here, we review the genetic architecture of AMD, considering the contribution of both common and rare alleles to susceptibility, and we explore the possible mechanistic links between photoreceptor degeneration and the alternative complement pathway, a cascade that has emerged as the most potent genetic driver of this disorder.

Electrical deregulation

International Nuclear Information System (INIS)

Simpson, R.

2001-01-01

Deregulation in the electricity sector took effect on January 1, 2001 in Alberta. Business consumers discovered that their electricity rates had almost doubled in a one-month period. The government argued that it was the case of short term pain for long term gain. The intent of the deregulation is the lowering of prices through competition. This principle applies when the supply meets the demand, but when the demand exceeds the supply, prices increase. When initial plans were made for the deregulation of the sector, utilities did not invest huge amounts of capital to build new generation plants, as it was not known how they would fare in the deregulated environment. This situation was compounded by the fact that there was an economic boom around the same time in Alberta, adding to the demands made on the existing generation infrastructure (approximately 4 per cent per year over the past decade). At the moment, some resource developers such as Syncrude, Amoco, and Daishowa produce their own electricity and export their excess capacity to the provincial grid for general use. The rules of the deregulated market have been clarified and a number of utilities are planning new generation plants and facilities. TransAlta, EPCOR, and Enmax Corp. have announced plans to expand or build new coal-fired plants. Alberta has an estimated 35 billion tonnes of recoverable coal, and 25 million tonnes of coal were used in 1999 to produce 75 per cent of the electricity required in Alberta. Over the next ten years, 4,000 megawatts of new capacity is planned, representing a 50 per cent increase over current levels. AES Corporation, a Virginia power giant, has also announced plans to build a generator in Alberta

Systematic Analysis Reveals that Cancer Mutations Converge on Deregulated Metabolism of Arachidonate and Xenobiotics

Directory of Open Access Journals (Sweden)

Francesco Gatto

2016-07-01

Full Text Available Mutations are the basis of the clonal evolution of most cancers. Nevertheless, a systematic analysis of whether mutations are selected in cancer because they lead to the deregulation of specific biological processes independent of the type of cancer is still lacking. In this study, we correlated the genome and transcriptome of 1,082 tumors. We found that nine commonly mutated genes correlated with substantial changes in gene expression, which primarily converged on metabolism. Further network analyses circumscribed the convergence to a network of reactions, termed AraX, that involves the glutathione- and oxygen-mediated metabolism of arachidonic acid and xenobiotics. In an independent cohort of 4,462 samples, all nine mutated genes were consistently correlated with the deregulation of AraX. Among all of the metabolic pathways, AraX deregulation represented the strongest predictor of patient survival. These findings suggest that oncogenic mutations drive a selection process that converges on the deregulation of the AraX network.

Sodium polyanethole sulfonate as an inhibitor of activation of complement function in blood culture systems

DEFF Research Database (Denmark)

Palarasah, Yaseelan; Skjoedt, Mikkel-Ole; Vitved, Lars

2010-01-01

complement activation pathways: the classical, alternative, and lectin pathways, respectively. Inhibition of complement activity by SPS is caused by a blocking of complement activation and is not a result of complement consumption. The classical pathway is inhibited at SPS concentrations greater than 0.1 mg...... findings also open up the possibility of a new assay for the assessment of the functional capacity of the lectin complement pathway....

Human T-Cell Leukemia Virus Type 1 Tax-Deregulated Autophagy Pathway and c-FLIP Expression Contribute to Resistance against Death Receptor-Mediated Apoptosis

Science.gov (United States)

Wang, Weimin; Zhou, Jiansuo; Shi, Juan; Zhang, Yaxi; Liu, Shilian

2014-01-01

ABSTRACT The human T-cell leukemia virus type 1 (HTLV-1) Tax protein is considered to play a central role in the process that leads to adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-1 Tax-expressing cells show resistance to apoptosis induced by Fas ligand (FasL) and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL). The regulation of Tax on the autophagy pathway in HeLa cells and peripheral T cells was recently reported, but the function and underlying molecular mechanism of the Tax-regulated autophagy are not yet well defined. Here, we report that HTLV-1 Tax deregulates the autophagy pathway, which plays a protective role during the death receptor (DR)-mediated apoptosis of human U251 astroglioma cells. The cellular FLICE-inhibitory protein (c-FLIP), which is upregulated by Tax, also contributes to the resistance against DR-mediated apoptosis. Both Tax-induced autophagy and Tax-induced c-FLIP expression require Tax-induced activation of IκB kinases (IKK). Furthermore, Tax-induced c-FLIP expression is regulated through the Tax-IKK-NF-κB signaling pathway, whereas Tax-triggered autophagy depends on the activation of IKK but not the activation of NF-κB. In addition, DR-mediated apoptosis is correlated with the degradation of Tax, which can be facilitated by the inhibitors of autophagy. IMPORTANCE Our study reveals that Tax-deregulated autophagy is a protective mechanism for DR-mediated apoptosis. The molecular mechanism of Tax-induced autophagy is also illuminated, which is different from Tax-increased c-FLIP. Tax can be degraded via manipulation of autophagy and TRAIL-induced apoptosis. These results outline a complex regulatory network between and among apoptosis, autophagy, and Tax and also present evidence that autophagy represents a new possible target for therapeutic intervention for the HTVL-1 related diseases. PMID:24352466

Evidence for the Deregulation of Protein Turnover Pathways in Atm-Deficient Mouse Cerebellum: An Organotypic Study.

Science.gov (United States)

Kim, Catherine D; Reed, Ryan E; Juncker, Meredith A; Fang, Zhide; Desai, Shyamal D

2017-07-01

Interferon-stimulated gene 15 (ISG15), an antagonist of the ubiquitin pathway, is elevated in cells and brain tissues obtained from ataxia telangiectasia (A-T) patients. Previous studies reveal that an elevated ISG15 pathway inhibits ubiquitin-dependent protein degradation, leading to activation of basal autophagy as a compensatory mechanism for protein turnover in A-T cells. Also, genotoxic stress (ultraviolet [UV] radiation) deregulates autophagy and induces aberrant degradation of ubiquitylated proteins in A-T cells. In the current study, we show that, as in A-T cells, ISG15 protein expression is elevated in cerebellums and various other tissues obtained from Atm-compromised mice in an Atm-allele-dependent manner (Atm+/+ Atm+/- Atm-/-). Notably, in cerebellums, the brain part primarily affected in A-T, levels of ISG15 were significantly greater (3-fold higher) than cerebrums obtained from the same set of mice. Moreover, as in A-T cell culture, UV induces aberrant degradation of ubiquitylated proteins and autophagy in Atm-deficient, but not in Atm-proficient, cerebellar brain slices grown in culture. Thus, the ex vivo organotypic A-T mouse brain culture model mimics that of an A-T human cell culture model and could be useful for studying the role of ISG15-dependent proteinopathy in cerebellar neurodegeneration, a hallmark of A-T in humans. © 2017 American Association of Neuropathologists, Inc. All rights reserved.

New perspectives on mannan-binding lectin-mediated complement activation

DEFF Research Database (Denmark)

Degn, Søren Egedal; Thiel, Steffen; Jensenius, Jens Christian

2007-01-01

The complement system is an important part of the innate immune system, mediating several major effector functions and modulating adaptive immune responses. Three complement activation pathways exist: the classical pathway (CP), the alternative pathway (AP), and the lectin pathway (LP). The LP......, allowing C3 activation in the absence of components otherwise believed critical. The classical bypass pathways are dependent on C1 and components of the AP. A recent study has shown the existence also of a lectin bypass pathway dependent on mannan-binding lectin (MBL) and AP components. The emerging...

Deregulation of the ubiquitin-proteasome system is the predominant molecular pathology in OPMD animal models and patients

DEFF Research Database (Denmark)

Anvar, Seyed Yahya; hoen, Peter Ac; Venema, Andrea

2011-01-01

molecular pathways that are consistently associated with OPMD, we performed an integrated high-throughput transcriptome study in affected muscles of OPMD animal models and patients. The ubiquitin-proteasome system (UPS) was found to be the most consistently and significantly OPMD-deregulated pathway across...

Complement in patients receiving maintenance hemodialysis: functional screening and quantitative analysis

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Horikoshi Satoshi

2010-12-01

Full Text Available Abstract Background The complement system is vital for innate immunity and is implicated in the pathogenesis of inflammatory diseases and the mechanism of host defense. Complement deficiencies occasionally cause life-threatening diseases. In hemodialysis (HD patients, profiles on complement functional activity and deficiency are still obscure. The objectives of the present study were to measure the functional complement activities of the classical pathway (CP, lectin pathway (LP and alternative pathway (AP using a novel method and consequently to elucidate the rates of deficiencies among HD patients. Methods In the present study, 244 HD patients at one dialysis center and 204 healthy controls were enrolled. Functional complement activities were measured simultaneously using the Wielisa®-kit. The combination of the results of these three pathway activities allows us to speculate which candidate complement is deficient; subsequently, the deficient complement was determined. Results All three functional complement activities were significantly higher in the HD patients than in the control group (P ®-kit, 16 sera (8.8% with mannose-binding lectin (MBL deficiency, 1 serum (0.4% with C4 deficiency, 1 serum (0.4% with C9 deficiency, and 1 serum (0.4% with B deficiency were observed in the HD group, and 18 sera (8.8% with MBL deficiency and 1 serum (0.5% with B deficiency were observed in the control group. There were no significant differences in the 5-year mortality rate between each complement-deficient group and the complement-sufficient group among the HD patients. Conclusion This is the first report that profiles complement deficiencies by simultaneous measurement of functional activities of the three complement pathways in HD patients. Hemodialysis patients frequently suffer from infections or malignancies, but functional complement deficiencies do not confer additional risk of mortality.

The undertow of deregulation : reregulation

International Nuclear Information System (INIS)

Bradford, J.A.

2003-01-01

Alberta, Ontario and New Brunswick each initiated measures to deregulate their electric power industries in order to remain competitive with lower electricity rates in some U.S. states where the industry was also moving towards deregulation. This paper considers how the original sweep of deregulation policy goals succumbed to electricity reregulation policies. The decision by British Columbia to re-examine its deregulation plans in light of the experience in Canada's 3 other province's was also examined. The paper describes the electric power industry from 1900 to 1960s, before the deregulation wave hit the industry. It then proceeds to the 1970s which was marked by the oil embargo. The 1980s saw a new era of policy shifts towards deregulation and privatization activity which was intended to introduce competition into regulated industries. Alberta was the first Canadian province to introduce competition to its electricity industry in an effort to remain competitive with neighbouring U.S. jurisdictions. By the 1990s Ontario's vertically integrated electricity industry was in trouble and recommendations were made to dissolve Ontario's Hydro One monopoly, particularly in power generation. In 1999, New Brunswick restructured its electricity industry to remain competitive with New England's electricity industry. The paper describes the gradual pull back from deregulation by all 3 provinces and the measures taken to impose price controls. Both industry and consumers paid a price for major policy changes. Complete competition in New Brunswick never materialized. It was suggested that controlled competition will likely move the electricity industry in the future. 40 refs

Sex-specific patterns and deregulation of endocrine pathways in the gene expression profiles of Bangladeshi adults exposed to arsenic contaminated drinking water

Energy Technology Data Exchange (ETDEWEB)

Muñoz, Alexandra; Chervona, Yana [New York University School of Medicine, Nelson Institute of Environmental Medicine, Tuxedo, NY (United States); Hall, Megan [Department of Epidemiology, Mailman School of Public Health, Columbia University, New York (United States); Kluz, Thomas [New York University School of Medicine, Nelson Institute of Environmental Medicine, Tuxedo, NY (United States); Gamble, Mary V., E-mail: mvg7@columbia.edu [Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York (United States); Costa, Max, E-mail: Max.Costa@nyumc.org [New York University School of Medicine, Nelson Institute of Environmental Medicine, Tuxedo, NY (United States)

2015-05-01

biological implications. • Both sexes exhibit deregulation of cardiovascular and endocrine pathways.

Sex-specific patterns and deregulation of endocrine pathways in the gene expression profiles of Bangladeshi adults exposed to arsenic contaminated drinking water

International Nuclear Information System (INIS)

Muñoz, Alexandra; Chervona, Yana; Hall, Megan; Kluz, Thomas; Gamble, Mary V.; Costa, Max

2015-01-01

biological implications. • Both sexes exhibit deregulation of cardiovascular and endocrine pathways

Inhibition of the alternative complement activation pathway in traumatic brain injury by a monoclonal anti-factor B antibody: a randomized placebo-controlled study in mice

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Holers V Michael

2007-05-01

Full Text Available Abstract Background The posttraumatic response to traumatic brain injury (TBI is characterized, in part, by activation of the innate immune response, including the complement system. We have recently shown that mice devoid of a functional alternative pathway of complement activation (factor B-/- mice are protected from complement-mediated neuroinflammation and neuropathology after TBI. In the present study, we extrapolated this knowledge from studies in genetically engineered mice to a pharmacological approach using a monoclonal anti-factor B antibody. This neutralizing antibody represents a specific and potent inhibitor of the alternative complement pathway in mice. Methods A focal trauma was applied to the left hemisphere of C57BL/6 mice (n = 89 using a standardized electric weight-drop model. Animals were randomly assigned to two treatment groups: (1 Systemic injection of 1 mg monoclonal anti-factor B antibody (mAb 1379 in 400 μl phosphate-buffered saline (PBS at 1 hour and 24 hours after trauma; (2 Systemic injection of vehicle only (400 μl PBS, as placebo control, at identical time-points after trauma. Sham-operated and untreated mice served as additional negative controls. Evaluation of neurological scores and analysis of brain tissue specimens and serum samples was performed at defined time-points for up to 1 week. Complement activation in serum was assessed by zymosan assay and by murine C5a ELISA. Brain samples were analyzed by immunohistochemistry, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL histochemistry, and real-time RT-PCR. Results The mAb 1379 leads to a significant inhibition of alternative pathway complement activity and to significantly attenuated C5a levels in serum, as compared to head-injured placebo-treated control mice. TBI induced histomorphological signs of neuroinflammation and neuronal apoptosis in the injured brain hemisphere of placebo-treated control mice for up to 7 days. In contrast, the

Molluskan Hemocyanins Activate the Classical Pathway of the Human Complement System through Natural Antibodies.

Science.gov (United States)

Pizarro-Bauerle, Javier; Maldonado, Ismael; Sosoniuk-Roche, Eduardo; Vallejos, Gerardo; López, Mercedes N; Salazar-Onfray, Flavio; Aguilar-Guzmán, Lorena; Valck, Carolina; Ferreira, Arturo; Becker, María Inés

2017-01-01

Molluskan hemocyanins are enormous oxygen-carrier glycoproteins that show remarkable immunostimulatory properties when inoculated in mammals, such as the generation of high levels of antibodies, a strong cellular reaction, and generation of non-specific antitumor immune responses in some types of cancer, particularly for superficial bladder cancer. These proteins have the ability to bias the immune response toward a T h 1 phenotype. However, despite all their current uses with beneficial clinical outcomes, a clear mechanism explaining these properties is not available. Taking into account reports of natural antibodies against the hemocyanin of the gastropod Megathura crenulata [keyhole limpet hemocyanin (KLH)] in humans as well as other vertebrate species, we report here for the first time, the presence, in sera from unimmunized healthy donors, of antibodies recognizing, in addition to KLH, two other hemocyanins from gastropods with documented immunomodulatory capacities: Fisurella latimarginata hemocyanin (FLH) and Concholepas concholepas hemocyanin (CCH). Through an ELISA screening, we found IgM and IgG antibodies reactive with these hemocyanins. When the capacity of these antibodies to bind deglycosylated hemocyanins was studied, no decreased interaction was detected. Moreover, in the case of FLH, deglycosylation increased antibody binding. We evaluated through an in vitro complement deposition assay whether these antibodies activated the classical pathway of the human complement system. The results showed that all three hemocyanins and their deglycosylated counterparts elicited this activation, mediated by C1 binding to immunoglobulins. Thus, this work contributes to the understanding on how the complement system could participate in the immunostimulatory properties of hemocyanins, through natural, complement-activating antibodies reacting with these proteins. Although a role for carbohydrates cannot be completely ruled out, in our experimental setting

The salivary scavenger and agglutinin (SALSA binds MBL and regulates the lectin pathway of complement in solution and on surfaces

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Martin eParnov Reichhardt

2012-07-01

Full Text Available The scavenger receptor cysteine-rich (SRCR protein SALSA, also known as gp340, salivary agglutinin (SAG and deleted in malignant brain tumor 1 (DMBT1, is a 340 kDa glycoprotein expressed on mucosal surfaces and secreted into several body fluids. SALSA binds to a broad variety of microbes and endogenous ligands, such as complement factor C1q, surfactant proteins D and A (SP-D and SP-A and IgA. Our search for novel ligands of SALSA by direct protein-interaction studies led to the identification of mannan binding lectin (MBL as a new binding partner. We observed that surface-associated SALSA activates complement via binding of MBL. On the other hand, soluble SALSA was found to inhibit C. albicans-induced complement activation. Thus, SALSA has a dual complement regulatory function. It activates the lectin pathway when bound to a surface and inhibits it when free in the fluid-phase. These activities are mediated via a direct interaction with MBL.

Surviving mousepox infection requires the complement system.

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Elizabeth A Moulton

2008-12-01

Full Text Available Poxviruses subvert the host immune response by producing immunomodulatory proteins, including a complement regulatory protein. Ectromelia virus provides a mouse model for smallpox where the virus and the host's immune response have co-evolved. Using this model, our study investigated the role of the complement system during a poxvirus infection. By multiple inoculation routes, ectromelia virus caused increased mortality by 7 to 10 days post-infection in C57BL/6 mice that lack C3, the central component of the complement cascade. In C3(-/- mice, ectromelia virus disseminated earlier to target organs and generated higher peak titers compared to the congenic controls. Also, increased hepatic inflammation and necrosis correlated with these higher tissue titers and likely contributed to the morbidity in the C3(-/- mice. In vitro, the complement system in naïve C57BL/6 mouse sera neutralized ectromelia virus, primarily through the recognition of the virion by natural antibody and activation of the classical and alternative pathways. Sera deficient in classical or alternative pathway components or antibody had reduced ability to neutralize viral particles, which likely contributed to increased viral dissemination and disease severity in vivo. The increased mortality of C4(-/- or Factor B(-/- mice also indicates that these two pathways of complement activation are required for survival. In summary, the complement system acts in the first few minutes, hours, and days to control this poxviral infection until the adaptive immune response can react, and loss of this system results in lethal infection.

Cyclosporine Induces Endothelial Cell Release of Complement-Activating Microparticles

Science.gov (United States)

Renner, Brandon; Klawitter, Jelena; Goldberg, Ryan; McCullough, James W.; Ferreira, Viviana P.; Cooper, James E.; Christians, Uwe

2013-01-01

Defective control of the alternative pathway of complement is an important risk factor for several renal diseases, including atypical hemolytic uremic syndrome. Infections, drugs, pregnancy, and hemodynamic insults can trigger episodes of atypical hemolytic uremic syndrome in susceptible patients. Although the mechanisms linking these clinical events with disease flares are unknown, recent work has revealed that each of these clinical conditions causes cells to release microparticles. We hypothesized that microparticles released from injured endothelial cells promote intrarenal complement activation. Calcineurin inhibitors cause vascular and renal injury and can trigger hemolytic uremic syndrome. Here, we show that endothelial cells exposed to cyclosporine in vitro and in vivo release microparticles that activate the alternative pathway of complement. Cyclosporine-induced microparticles caused injury to bystander endothelial cells and are associated with complement-mediated injury of the kidneys and vasculature in cyclosporine-treated mice. Cyclosporine-induced microparticles did not bind factor H, an alternative pathway regulatory protein present in plasma, explaining their complement-activating phenotype. Finally, we found that in renal transplant patients, the number of endothelial microparticles in plasma increases 2 weeks after starting tacrolimus, and treatment with tacrolimus associated with increased C3 deposition on endothelial microparticles in the plasma of some patients. These results suggest that injury-associated release of endothelial microparticles is an important mechanism by which systemic insults trigger intravascular complement activation and complement-dependent renal diseases. PMID:24092930

Assembly and activation of alternative complement components on endothelial cell-anchored ultra-large von Willebrand factor links complement and hemostasis-thrombosis.

Directory of Open Access Journals (Sweden)

Nancy A Turner

Full Text Available Vascular endothelial cells (ECs express and release protein components of the complement pathways, as well as secreting and anchoring ultra-large von Willebrand factor (ULVWF multimers in long string-like structures that initiate platelet adhesion during hemostasis and thrombosis. The alternative complement pathway (AP is an important non-antibody-requiring host defense system. Thrombotic microangiopathies can be associated with defective regulation of the AP (atypical hemolytic-uremic syndrome or with inadequate cleavage by ADAMTS-13 of ULVWF multimeric strings secreted by/anchored to ECs (thrombotic thrombocytopenic purpura. Our goal was to determine if EC-anchored ULVWF strings caused the assembly and activation of AP components, thereby linking two essential defense mechanisms.We quantified gene expression of these complement components in cultured human umbilical vein endothelial cells (HUVECs by real-time PCR: C3 and C5; complement factor (CF B, CFD, CFP, CFH and CFI of the AP; and C4 of the classical and lectin (but not alternative complement pathways. We used fluorescent microscopy, monospecific antibodies against complement components, fluorescent secondary antibodies, and the analysis of >150 images to quantify the attachment of HUVEC-released complement proteins to ULVWF strings secreted by, and anchored to, the HUVECs (under conditions of ADAMTS-13 inhibition. We found that HUVEC-released C4 did not attach to ULVWF strings, ruling out activation of the classical and lectin pathways by the strings. In contrast, C3, FB, FD, FP and C5, FH and FI attached to ULVWF strings in quantitative patterns consistent with assembly of the AP components into active complexes. This was verified when non-functional FB blocked the formation of AP C3 convertase complexes (C3bBb on ULVWF strings.AP components are assembled and activated on EC-secreted/anchored ULVWF multimeric strings. Our findings provide one possible molecular mechanism for clinical

Ficolin-3-mediated lectin complement pathway activation in patients with subarachnoid hemorrhage

DEFF Research Database (Denmark)

Zanier, Elisa R; Zangari, Rosalia; Munthe-Fog, Lea

2014-01-01

OBJECTIVES: To assess the involvement of ficolin-3, the main initiator of the lectin complement pathway (LCP), in subarachnoid hemorrhage (SAH) pathology and outcome. METHODS: In this preliminary exploratory study, plasma concentration of ficolin-3 and of ficolin-3-mediated functional LCP activity...... the World Federation of Neurosurgical Societies grading scale; vasospasm, defined as neuro-worsening with angiographic confirmation of vessel narrowing; cerebral ischemia, defined as hypodense lesion on CT scan performed before discharge; and 6-month outcome, assessed using the Glasgow Outcome Scale....... RESULTS: In patients, no changes were detected for ficolin-3 compared with controls. Notably, however, ficolin-3-mediated functional LCP activity was reduced. Low levels of plasma ficolin-3 and ficolin-3-mediated functional LCP activity were related to SAH severity, vasospasm, and cerebral ischemia...

Early Components of the Complement Classical Activation Pathway in Human Systemic Autoimmune Diseases

Science.gov (United States)

Lintner, Katherine E.; Wu, Yee Ling; Yang, Yan; Spencer, Charles H.; Hauptmann, Georges; Hebert, Lee A.; Atkinson, John P.; Yu, C. Yung

2016-01-01

The complement system consists of effector proteins, regulators, and receptors that participate in host defense against pathogens. Activation of the complement system, via the classical pathway (CP), has long been recognized in immune complex-mediated tissue injury, most notably systemic lupus erythematosus (SLE). Paradoxically, a complete deficiency of an early component of the CP, as evidenced by homozygous genetic deficiencies reported in human, are strongly associated with the risk of developing SLE or a lupus-like disease. Similarly, isotype deficiency attributable to a gene copy-number (GCN) variation and/or the presence of autoantibodies directed against a CP component or a regulatory protein that result in an acquired deficiency are relatively common in SLE patients. Applying accurate assay methodologies with rigorous data validations, low GCNs of total C4, and heterozygous and homozygous deficiencies of C4A have been shown as medium to large effect size risk factors, while high copy numbers of total C4 or C4A as prevalent protective factors, of European and East-Asian SLE. Here, we summarize the current knowledge related to genetic deficiency and insufficiency, and acquired protein deficiencies for C1q, C1r, C1s, C4A/C4B, and C2 in disease pathogenesis and prognosis of SLE, and, briefly, for other systemic autoimmune diseases. As the complement system is increasingly found to be associated with autoimmune diseases and immune-mediated diseases, it has become an attractive therapeutic target. We highlight the recent developments and offer a balanced perspective concerning future investigations and therapeutic applications with a focus on early components of the CP in human systemic autoimmune diseases. PMID:26913032

Soluble Collectin-12 (CL-12) Is a Pattern Recognition Molecule Initiating Complement Activation via the Alternative Pathway

DEFF Research Database (Denmark)

Ma, Ying Jie; Hein, Estrid; Munthe-Fog, Lea

2015-01-01

and may recognize certain bacteria and fungi, leading to opsonophagocytosis. However, based on its structural and functional similarities with soluble collectins, we hypothesized the existence of a fluid-phase analog of CL-12 released from cells, which may function as a soluble pattern-recognition...... of the terminal complement complex. These results demonstrate the existence of CL-12 in a soluble form and indicate a novel mechanism by which the alternative pathway of complement may be triggered directly by a soluble pattern-recognition molecule....... nonreducing conditions it presented multimeric assembly forms. Immunoprecipitation and Western blot analysis of human umbilical cord plasma enabled identification of a natural soluble form of CL-12 having an electrophoretic mobility pattern close to that of shed soluble recombinant CL-12. Soluble CL-12 could...

Environmental impact of electricity deregulation

International Nuclear Information System (INIS)

Swisher, Joel N.; McAlpin, Maria C.

2006-01-01

Restructuring of electric utilities affects environmental quality primarily through its effect on airborne emissions. We examine emissions from 1993 to 2002 and discuss possible explanatory factors. Annual NOx and SO 2 emissions fell nationally, mostly due to decreases in emission limits driven by state and Federal regulations. CO 2 emissions have increased almost proportionately with increased generation. Generation increased more than it would have, partly due to energy efficiency spending reductions that accompanied deregulation. The fuel mix shifted slightly from coal to gas, offsetting some CO 2 emissions increases and contributing to SO 2 and NOx emissions decreases. While the percentage share of generation from renewable sources remained at about 2%, recent and expected future increases in wind generating capacity promise future emissions reductions. Although deregulation lacks clear environmental advantages, the deregulation process creates an opportunity for implementation of state policies to reduce emissions. Regulated and deregulated states with renewable portfolio standards (RPS) have a higher average percent of generation from renewable sources. Average energy efficiency savings are higher in regulated states, but slightly higher in deregulated states with a system benefits charge (SBC) than in regulated states without a SBC

Deregulated microRNAs in CD4+ T cells from individuals with latent tuberculosis versus active tuberculosis.

Science.gov (United States)

Fu, Yurong; Yi, Zhengjun; Li, Jianhua; Li, Ruifang

2014-03-01

The mechanisms of latent tuberculosis (TB) infection remain elusive. Roles of microRNA (miRNA) have been highlighted in pathogen-host interactions recently. To identify miRNAs involved in the immune response to TB, expression profiles of miRNAs in CD4(+) T cells from patients with latent TB, active TB and healthy controls were investigated by microarray assay and validated by RT-qPCR. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used to analyse the significant functions and involvement in signalling pathways of the differentially expressed miRNAs. To identify potential target genes for miR-29, interferon-γ (IFN-γ) mRNA expression was measured by RT-qPCR. Our results showed that 27 miRNAs were deregulated among the three groups. RT-qPCR results were generally consistent with the microarray data. We observed an inverse correlation between miR-29 level and IFN-γ mRNA expression in CD4(+) T cells. GO and KEGG pathway analysis showed that the possible target genes of deregulated miRNAs were significantly enriched in mitogen-activated protein kinase signalling pathway, focal adhesion and extracellular matrix receptor interaction, which might be involved in the transition from latent to active TB. In all, for the first time, our study revealed that some miRNAs in CD4(+) T cells were altered in latent and active TB. Function and pathway analysis highlighted the possible involvement of miRNA-deregulated mRNAs in TB. The study might help to improve understanding of the relationship between miRNAs in CD4(+) T cells and TB, and laid an important foundation for further identification of the underlying mechanisms of latent TB infection and its reactivation. © 2013 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Power deregulation in Alberta

International Nuclear Information System (INIS)

MacMurchy, N.E.

1999-01-01

The impacts of deregulation of the electric power industry in Alberta from the perspective of the natural gas industry was presented with special focus on how the power market can be brought back into balance. The issue of what impacts the deregulated power market will have on natural gas consumption or prices was also reviewed. It was noted that deregulation of the electric power industry will have a definite impact on natural gas consumption but no significant impact on prices. It is estimated that in 1999/2000 gas demand will be 90 million cf/day for incremental electricity generation. However, as long as pipe capacity out of the province exits, this increase in natural gas demand in Alberta is not expected to affect gas prices

Deregulating electricity in the American states

Science.gov (United States)

Terbush, Thomas Lee

This dissertation develops nine stylized facts that summarize the major consequences of deregulation and tests these against recent experience in the electric utility industry. The experience of the electric utility industry matches the predictions of the stylized facts, except in one instance: although real electricity prices fell between 1982 and 1999, real prices fell less in states that deregulated. This dissertation presents three possible explanations for this discrepancy. First, through dynamic efficiency, consumers may benefit in the long run through lower rates and better service in the electricity market, or deregulation may be a public good that benefits electricity consumers through economy-wide improvements in efficiency. Second, higher prices may be a long-run outcome as predicted by the theory of the second best. Or third, both regulators and utilities may use deregulation to generate new rents. Because the original rents from regulation had dissipated, new rents could be generated under deregulation by making consumers pay off the utilities and then creating more new rents through re-regulation of the industry. Close examination tends to support the first and third explanations, although the second-best explanation cannot yet be ruled out completely. Higher prices appear to be a transitional phenomenon, resulting from a short-term payoff from consumers to incumbent utilities that was required to move deregulation forward. This payoff occurs as residential and commercial consumers bear relatively higher rates over three to five years to compensate utilities for stranded costs, investments thought to be unrecoverable under full competition. All states are benefiting from deregulation, but states that are deregulating are benefiting less while stranded costs are being recovered. This dissertation also examines California electricity deregulation and finds that the experience in California conforms with to the stylized facts, and that certain structural

Did Globalization Influence Credit Market Deregulation

OpenAIRE

Eppinger, Peter; Potrafke, Niklas

2015-01-01

We investigate whether globalization influenced credit market deregulation over the period 1970-2010. Globalization is measured by the KOF indices of globalization. Credit market deregulation is measured by the credit market freedom indicators of the Fraser Institute. The results from both cross-sectional and panel regressions using ordinary least squares indicate a positive correlation between globalization and credit market deregulation. We account for reverse causality by using predicted t...

Down-regulation of complement receptors on the surface of host monocyte even as in vitro complement pathway blocking interferes in dengue infection.

Directory of Open Access Journals (Sweden)

Cintia Ferreira Marinho

Full Text Available In dengue virus (DENV infection, complement system (CS activation appears to have protective and pathogenic effects. In severe dengue fever (DF, the levels of DENV non-structural-1 protein and of the products of complement activation, including C3a, C5a and SC5b-9, are higher before vascular leakage occurs, supporting the hypothesis that complement activation contributes to unfavourable outcomes. The clinical manifestations of DF range from asymptomatic to severe and even fatal. Here, we aimed to characterise CS by their receptors or activation product, in vivo in DF patients and in vitro by DENV-2 stimulation on monocytes. In comparison with healthy controls, DF patients showed lower expression of CR3 (CD11b, CR4 (CD11c and, CD59 on monocytes. The DF patients who were high producers of SC5b-9 were also those that showed more pronounced bleeding or vascular leakage. Those findings encouraged us to investigate the role of CS in vitro, using monocytes isolated from healthy subjects. Prior blocking with CR3 alone (CD11b or CR3 (CD11b/CD18 reduced viral infection, as quantified by the levels of intracellular viral antigen expression and soluble DENV non-structural viral protein. However, we found that CR3 alone (CD11b or CR3 (CD11b/CD18 blocking did not influence major histocompatibility complex presentation neither active caspase-1 on monocytes, thus probably ruling out inflammasome-related mechanisms. Although it did impair the secretion of tumour necrosis factor alpha and interferon alpha. Our data provide strategies of blocking CR3 (CD11b pathways could have implications for the treatment of viral infection by antiviral-related mechanisms.

Natural gas deregulation

International Nuclear Information System (INIS)

Ronchi, M.

1993-01-01

With the aim of establishing realistic options for deregulation in the natural gas industry, this paper first considers the structural evolution of this industry and evidences how it differs from the petroleum industry with which it exhibits some essential characteristics in common. This comparison is made in order to stress that, contrary to popular belief, that which is without doubt good for the petroleum industry is not necessarily so also for the natural gas industry. The paper concludes with separate analyses of the natural gas markets in the principal industrialized countries. Arguments are provided to show that the 'soft' deregulation option for the natural gas industry is not feasible, and that 'total' deregulation instead, backed by the passing of a suitable package of anti-trust laws 'unbundling' the industry's four major activities, i.e., production, storage, primary and secondary distribution, is the preferable option. The old concept of guaranteed supplies for minor users of natural gas should give way to the laws of supply and demand governing inter-fuel competition ensured through the strict supervision of vigilance committees

Activation and binding of opsonic fragments of C3 on encapsulated Cryptococcus neoformans by using an alternative complement pathway reconstituted from six isolated proteins.

Science.gov (United States)

Kozel, T R; Wilson, M A; Pfrommer, G S; Schlageter, A M

1989-07-01

Encapsulated Cryptococcus neoformans yeast cells are potent activators of the complement system. We examined the interaction of the yeast cells with an alternative complement pathway reconstituted from isolated factor D, factor B, factor H, factor I, C3, and properdin. Incubation of encapsulated cryptococci with the reconstituted pathway led to activation and binding of C3 fragments to the yeast cells that was quantitatively and qualitatively identical to that observed with normal human serum. Incubation with either normal serum or a mixture of isolated proteins led to binding of 4 x 10(7) to 5 x 10(7) C3 molecules to the yeast cells. The kinetics for activation and binding of C3 were identical, with maximum binding observed after a 20-min incubation. Immunoglobulin G was not needed for optimal activation kinetics. C3 fragments eluted from the yeast cells by treatment with hydroxylamine and subsequent analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis demonstrated the presence primarily of iC3b on yeast cells incubated with either normal serum or the reconstituted pathway. Ultrastructural examination of the opsonized yeast cells showed that the cryptococcal capsule was the site for binding of C3 activated from normal serum or the reconstituted pathway, with a dense accumulation of C3 at the periphery of the capsule. Thus, incubation of encapsulated cryptococci in the reconstituted pathway led to deposition of opsonic complement fragments at a site that was appropriate for interaction with phagocyte receptors. Cryptococci opsonized with the reconstituted pathway showed a markedly enhanced interaction with cultured human monocytes compared with unopsonized yeast cells, indicating that the alternative pathway alone is opsonic for yeast cells. However, the results indicate that additional serum factors are needed for optimal opsonization of yeast cells because a 35% reduction in the number of cryptococci bound to macrophages was observed with

Activation capacity of the alternative and classic complement pathways in patients operated on for colorectal cancer

DEFF Research Database (Denmark)

Zimmermann-Nielsen, Erik; Iversen, Lene H; Svehag, Sven-Erik

2002-01-01

surgery. The samples were analyzed with an enzyme-linked immunosorbent assay that measured C3 activation capacity by the alternative and classic complement pathways. Cancer patients were compared according to Dukes stage, type of surgery performed, transfusion of blood, development of infection, venous....... Significant differences in C3 activation capacities were observed between cancer patients that were related to Dukes stage and in patients with and without buffy coat-depleted red cells suspended in saline, adenine, glucose, and mannitol transfusion, infectious events, and deep venous thromboembolism...

Natural gas and deregulation

International Nuclear Information System (INIS)

Maisonnier, G.

2001-01-01

The gas market is progressively moving towards new organizations under the effect of the deregulation initiated in the United States, the United Kingdom and transposed to other countries, particularly in Europe, at least for the member countries of the European union. Within the framework provided by this overall trend, Cedigaz proposes this study in order to describe the main developments affecting these markets on account of deregulation. This report is structured on the basis of three main topics (market organization, marketing modes, pricing) which appear to be the most cogent in terms of deregulation. This grouping by major topics accordingly offers a relatively synthetic view of the main trends which could be observed on the European market, for example. Our analysis is largely based on the example of the American market and, to a lesser extent, on the British situation. Whenever possible, concrete examples are provided for a closer understanding of this complex subject. On the whole, deregulation is not a frozen process, but has to adapt permanently to developments in a market stage-managed by politics, the regulator and the industrial players. This obviously means a dynamic and constantly evolving process, making it a highly complex process. This report aims to shed some light on the subject. (author)

Product Market Deregulation and Employment Outcomes

OpenAIRE

Senftleben-König, Charlotte

2014-01-01

This paper investigates the short- and medium-term effects of the deregulation of shopopening hours legislation on retail employment in Germany. In 2006, the legislative competence was shifted from the federal to the state level, leading to a gradual deregulation of shop opening restrictions in most of Germany’s sixteen federal states. The paper exploits regional variation in the legislation in order to identify the effect product market deregulation has on retail employment. We find robust e...

Intracellular Complement Activation Sustains T Cell Homeostasis and Mediates Effector Differentiation

Science.gov (United States)

Liszewski, M. Kathryn; Kolev, Martin; Le Friec, Gaelle; Leung, Marilyn; Bertram, Paula G.; Fara, Antonella F.; Subias, Marta; Pickering, Matthew C.; Drouet, Christian; Meri, Seppo; Arstila, T. Petteri; Pekkarinen, Pirkka T.; Ma, Margaret; Cope, Andrew; Reinheckel, Thomas; Rodriguez de Cordoba, Santiago; Afzali, Behdad; Atkinson, John P.; Kemper, Claudia

2013-01-01

Summary Complement is viewed as a critical serum-operative component of innate immunity, with processing of its key component, C3, into activation fragments C3a and C3b confined to the extracellular space. We report here that C3 activation also occurred intracellularly. We found that the T cell-expressed protease cathepsin L (CTSL) processed C3 into biologically active C3a and C3b. Resting T cells contained stores of endosomal and lysosomal C3 and CTSL and substantial amounts of CTSL-generated C3a. While “tonic” intracellular C3a generation was required for homeostatic T cell survival, shuttling of this intracellular C3-activation-system to the cell surface upon T cell stimulation induced autocrine proinflammatory cytokine production. Furthermore, T cells from patients with autoimmune arthritis demonstrated hyperactive intracellular complement activation and interferon-γ production and CTSL inhibition corrected this deregulated phenotype. Importantly, intracellular C3a was observed in all examined cell populations, suggesting that intracellular complement activation might be of broad physiological significance. PMID:24315997

Relative Contribution of Cellular Complement Inhibitors CD59, CD46, and CD55 to Parainfluenza Virus 5 Inhibition of Complement-Mediated Neutralization

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Yujia Li

2018-04-01

Full Text Available The complement system is a part of the innate immune system that viruses need to face during infections. Many viruses incorporate cellular regulators of complement activation (RCA to block complement pathways and our prior work has shown that Parainfluenza virus 5 (PIV5 incorporates CD55 and CD46 to delay complement-mediated neutralization. In this paper, we tested the role of a third individual RCA inhibitor CD59 in PIV5 interactions with complement pathways. Using a cell line engineered to express CD59, we show that small levels of functional CD59 are associated with progeny PIV5, which is capable of blocking assembly of the C5b-C9 membrane attack complex (MAC. PIV5 containing CD59 (PIV5-CD59 showed increased resistance to complement-mediated neutralization in vitro comparing to PIV5 lacking regulators. Infection of A549 cells with PIV5 and RSV upregulated CD59 expression. TGF-beta treatment of PIV5-infected cells also increased cell surface CD59 expression and progeny virions were more resistant to complement-mediated neutralization. A comparison of individual viruses containing only CD55, CD46, or CD59 showed a potency of inhibiting complement-mediated neutralization, which followed a pattern of CD55 > CD46 > CD59.

Defining the complement biomarker profile of c3 glomerulopathy

DEFF Research Database (Denmark)

Zhang, Yuzhou; Nester, Carla M; Martin, Bertha

2014-01-01

BACKGROUND AND OBJECTIVES: C3 glomerulopathy (C3G) applies to a group of renal diseases defined by a specific renal biopsy finding: a dominant pattern of C3 fragment deposition on immunofluorescence. The primary pathogenic mechanism involves abnormal control of the alternative complement pathway......, although a full description of the disease spectrum remains to be determined. This study sought to validate and define the association of complement dysregulation with C3G and to determine whether specific complement pathway abnormalities could inform disease definition. DESIGN, SETTING, PARTICIPANTS......, & MEASUREMENTS: This study included 34 patients with C3G (17 with C3 glomerulonephritis [C3GN] and 17 with dense deposit disease [DDD]) diagnosed between 2008 and 2013 selected from the C3G Registry. Control samples (n=100) were recruited from regional blood drives. Nineteen complement biomarkers were assayed...

‘N-of-1-pathways’ unveils personal deregulated mechanisms from a single pair of RNA-Seq samples: towards precision medicine

Science.gov (United States)

Gardeux, Vincent; Achour, Ikbel; Li, Jianrong; Maienschein-Cline, Mark; Li, Haiquan; Pesce, Lorenzo; Parinandi, Gurunadh; Bahroos, Neil; Winn, Robert; Foster, Ian; Garcia, Joe G N; Lussier, Yves A

2014-01-01

Background The emergence of precision medicine allowed the incorporation of individual molecular data into patient care. Indeed, DNA sequencing predicts somatic mutations in individual patients. However, these genetic features overlook dynamic epigenetic and phenotypic response to therapy. Meanwhile, accurate personal transcriptome interpretation remains an unmet challenge. Further, N-of-1 (single-subject) efficacy trials are increasingly pursued, but are underpowered for molecular marker discovery. Method ‘N-of-1-pathways’ is a global framework relying on three principles: (i) the statistical universe is a single patient; (ii) significance is derived from geneset/biomodules powered by paired samples from the same patient; and (iii) similarity between genesets/biomodules assesses commonality and differences, within-study and cross-studies. Thus, patient gene-level profiles are transformed into deregulated pathways. From RNA-Seq of 55 lung adenocarcinoma patients, N-of-1-pathways predicts the deregulated pathways of each patient. Results Cross-patient N-of-1-pathways obtains comparable results with conventional genesets enrichment analysis (GSEA) and differentially expressed gene (DEG) enrichment, validated in three external evaluations. Moreover, heatmap and star plots highlight both individual and shared mechanisms ranging from molecular to organ-systems levels (eg, DNA repair, signaling, immune response). Patients were ranked based on the similarity of their deregulated mechanisms to those of an independent gold standard, generating unsupervised clusters of diametric extreme survival phenotypes (p=0.03). Conclusions The N-of-1-pathways framework provides a robust statistical and relevant biological interpretation of individual disease-free survival that is often overlooked in conventional cross-patient studies. It enables mechanism-level classifiers with smaller cohorts as well as N-of-1 studies. Software http://lussierlab.org/publications/N-of-1-pathways

Systemic complement activation in age-related macular degeneration.

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Hendrik P N Scholl

Full Text Available Dysregulation of the alternative pathway (AP of complement cascade has been implicated in the pathogenesis of age-related macular degeneration (AMD, the leading cause of blindness in the elderly. To further test the hypothesis that defective control of complement activation underlies AMD, parameters of complement activation in blood plasma were determined together with disease-associated genetic markers in AMD patients. Plasma concentrations of activation products C3d, Ba, C3a, C5a, SC5b-9, substrate proteins C3, C4, factor B and regulators factor H and factor D were quantified in patients (n = 112 and controls (n = 67. Subjects were analyzed for single nucleotide polymorphisms in factor H (CFH, factor B-C2 (BF-C2 and complement C3 (C3 genes which were previously found to be associated with AMD. All activation products, especially markers of chronic complement activation Ba and C3d (p<0.001, were significantly elevated in AMD patients compared to controls. Similar alterations were observed in factor D, but not in C3, C4 or factor H. Logistic regression analysis revealed better discriminative accuracy of a model that is based only on complement activation markers Ba, C3d and factor D compared to a model based on genetic markers of the complement system within our study population. In both the controls' and AMD patients' group, the protein markers of complement activation were correlated with CFH haplotypes.This study is the first to show systemic complement activation in AMD patients. This suggests that AMD is a systemic disease with local disease manifestation at the ageing macula. Furthermore, the data provide evidence for an association of systemic activation of the alternative complement pathway with genetic variants of CFH that were previously linked to AMD susceptibility.

A metalloproteinase karilysin present in the majority of Tannerella forsythia isolates inhibits all pathways of the complement system

DEFF Research Database (Denmark)

Jusko, Monika; Potempa, Jan; Karim, Abdulkarim Y

2012-01-01

Tannerella forsythia is a poorly studied pathogen despite being one of the main causes of periodontitis, which is an inflammatory disease of the supporting structures of the teeth. We found that despite being recognized by all complement pathways, T. forsythia is resistant to killing by human....... forsythia obtained from patients with periodontitis. Taken together, the newly characterized karilysin appears to be an important virulence factor of T. forsythia and might have several important implications for immune evasion....

Deregulation and Macroeconomic Drivers Of Foreign Direct ...

African Journals Online (AJOL)

Deregulation and Macroeconomic Drivers Of Foreign Direct Investment In Nigerian Agriculture (1970 -2009): An Econometric Analysis. ... The study showed that foreign exchange and the economic deregulation policy of Nigerian government ...

Deregulation: Implications for Community College Leaders.

Science.gov (United States)

Bender, Louis W.

1986-01-01

Looks at the ways in which the deregulation of business and industry may affect community colleges in the years ahead, using the banking industry as an illustration. Argues that the deregulation of higher education requires that community college leadership programs examine past assumptions and develop new strategies. (LAL)

Spontaneous deregulation

NARCIS (Netherlands)

Edelman, Benjamin; Geradin, Damien

Platform businesses such as Airbnb and Uber have risen to success partly by sidestepping laws and regulations that encumber their traditional competitors. Such rule flouting is what the authors call “spontaneous private deregulation,” and it’s happening in a growing number of industries. The authors

Utility deregulation and AMR technology

International Nuclear Information System (INIS)

Moore, G.

1991-01-01

This article reviews the effects of deregulation on other utilities and services and examines how the electric utilities can avoid the worst of these effects and capitalize of the best aspects of competition in achieving marketing excellence. The article presents deregulation as a customer service and underscores the need for utilities to learn to compete aggressively and intelligently and provide additional services available through technology such as automated meter reading

Site-targeted complement inhibition by a complement receptor 2-conjugated inhibitor (mTT30) ameliorates post-injury neuropathology in mouse brains.

Science.gov (United States)

Rich, Megan C; Keene, Chesleigh N; Neher, Miriam D; Johnson, Krista; Yu, Zhao-Xue; Ganivet, Antoine; Holers, V Michael; Stahel, Philip F

2016-03-23

Intracerebral complement activation after severe traumatic brain injury (TBI) leads to a cascade of neuroinflammatory pathological sequelae that propagate host-mediated secondary brain injury and adverse outcomes. There are currently no specific pharmacological agents on the market to prevent or mitigate the development of secondary cerebral insults after TBI. A novel chimeric CR2-fH compound (mTT30) provides targeted inhibition of the alternative complement pathway at the site of tissue injury. This experimental study was designed to test the neuroprotective effects of mTT30 in a mouse model of closed head injury. The administration of 500 μg mTT30 i.v. at 1 h, 4 h and 24 h after head injury attenuated complement C3 deposition in injured brains, reduced the extent of neuronal cell death, and decreased post-injury microglial activation, compared to vehicle-injected placebo controls. These data imply that site-targeted alternative pathway complement inhibition may represent a new promising therapeutic avenue for the future management of severe TBI. Copyright © 2016. Published by Elsevier Ireland Ltd.

Genetic, molecular and functional analyses of complement factor I deficiency

DEFF Research Database (Denmark)

Nilsson, S.C.; Trouw, L.A.; Renault, N.

2009-01-01

Complete deficiency of complement inhibitor factor I (FI) results in secondary complement deficiency due to uncontrolled spontaneous alternative pathway activation leading to susceptibility to infections. Current genetic examination of two patients with near complete FI deficiency and three patie...

Autocrine Effects of Tumor-Derived Complement

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Min Soon Cho

2014-03-01

Full Text Available We describe a role for the complement system in enhancing cancer growth. Cancer cells secrete complement proteins that stimulate tumor growth upon activation. Complement promotes tumor growth via a direct autocrine effect that is partially independent of tumor-infiltrating cytotoxic T cells. Activated C5aR and C3aR signal through the PI3K/AKT pathway in cancer cells, and silencing the PI3K or AKT gene in cancer cells eliminates the progrowth effects of C5aR and C3aR stimulation. In patients with ovarian or lung cancer, higher tumoral C3 or C5aR mRNA levels were associated with decreased overall survival. These data identify a role for tumor-derived complement proteins in promoting tumor growth, and they therefore have substantial clinical and therapeutic implications.

The undertow of de-regulation : re-regulation

International Nuclear Information System (INIS)

Bradford, J.A.

2003-01-01

Alberta, Ontario and New Brunswick each initiated steps to deregulate their electric power industries in order to remain competitive with lower electricity rates in certain American states where the industry was also moving towards deregulation. This paper considers how the original sweep of deregulation policy goals succumbed to electricity re regulation policies. The decision by British Columbia to re-examine its deregulation plans in light of the experience in Canada's 3 other province's was also examined. The paper describes the electric power industry from 1900 to 1960s, before the deregulation wave hit the industry and then proceeds to the 1970s which was marked by the oil embargo. The 1980s saw a new era of policy shifts towards deregulation and privatization activity which was intended to introduce competition into regulated industries. Technological advances were taking place in the electricity sector, improving the viability of small gas turbines and making cogeneration possible. In the 1990s, Alberta was the first Canadian province to introduce competition to its electricity industry in an effort to remain competitive with neighbouring U.S. jurisdictions. By the 1990s Ontario's vertically integrated electricity industry was in trouble and recommendations were made to dissolve Ontario's Hydro One monopoly, particularly in power generation. In 1999, New Brunswick restructured its electricity industry to remain competitive with New England's electricity industry. The paper describes the gradual pull back from deregulation by all three provinces and the measures taken to impose price controls. Both industry and consumers paid a price for major policy changes. Complete competition in New Brunswick never materialized. It was suggested that controlled competition will likely move the electricity industry in the future. 40 refs

Determinism and Contingency Shape Metabolic Complementation in an Endosymbiotic Consortium.

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Ponce-de-Leon, Miguel; Tamarit, Daniel; Calle-Espinosa, Jorge; Mori, Matteo; Latorre, Amparo; Montero, Francisco; Pereto, Juli

2017-01-01

Bacterial endosymbionts and their insect hosts establish an intimate metabolic relationship. Bacteria offer a variety of essential nutrients to their hosts, whereas insect cells provide the necessary sources of matter and energy to their tiny metabolic allies. These nutritional complementations sustain themselves on a diversity of metabolite exchanges between the cell host and the reduced yet highly specialized bacterial metabolism-which, for instance, overproduces a small set of essential amino acids and vitamins. A well-known case of metabolic complementation is provided by the cedar aphid Cinara cedri that harbors two co-primary endosymbionts, Buchnera aphidicola BCc and Ca . Serratia symbiotica SCc, and in which some metabolic pathways are partitioned between different partners. Here we present a genome-scale metabolic network (GEM) for the bacterial consortium from the cedar aphid i BSCc. The analysis of this GEM allows us the confirmation of cases of metabolic complementation previously described by genome analysis (i.e., tryptophan and biotin biosynthesis) and the redefinition of an event of metabolic pathway sharing between the two endosymbionts, namely the biosynthesis of tetrahydrofolate. In silico knock-out experiments with i BSCc showed that the consortium metabolism is a highly integrated yet fragile network. We also have explored the evolutionary pathways leading to the emergence of metabolic complementation between reduced metabolisms starting from individual, complete networks. Our results suggest that, during the establishment of metabolic complementation in endosymbionts, adaptive evolution is significant in the case of tryptophan biosynthesis, whereas vitamin production pathways seem to adopt suboptimal solutions.

Deregulation and competition in the electric utility marketplace

International Nuclear Information System (INIS)

Allen, J.E.

1995-01-01

This paper addresses the impact of deregulation and competition in the electric utility marketplace as an extension of the deregulation of the airlines, and natural gas, telephone and trucking industries. The topics of the paper include the events and circumstances leading to deregulation, those involved in the competition, and a scenario for how the industry will develop over the next 20 years

Complement receptor expression and activation of the complement cascade on B lymphocytes from patients with systemic lupus erythematosus (SLE)

DEFF Research Database (Denmark)

Marquart, H V; Svendsen, A; Rasmussen, J M

1995-01-01

It has previously been reported that the expression of the complement receptors, CR1 on erythrocytes and blood leucocytes and CR2 on B cells, is reduced in patients with SLE, and that the reduced expression of CR1 on erythrocytes is related to disease activity. We have earlier demonstrated...... that normal B cells are capable of activating the alternative pathway (AP) of complement in a CR2-dependent fashion. In this study we have investigated whether disturbances in this activity may be related to the altered phenotype of SLE B cells. Flow cytometry was used to measure expression of complement...

Complement is activated in progressive multiple sclerosis cortical grey matter lesions.

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Watkins, Lewis M; Neal, James W; Loveless, Sam; Michailidou, Iliana; Ramaglia, Valeria; Rees, Mark I; Reynolds, Richard; Robertson, Neil P; Morgan, B Paul; Howell, Owain W

2016-06-22

The symptoms of multiple sclerosis (MS) are caused by damage to myelin and nerve cells in the brain and spinal cord. Inflammation is tightly linked with neurodegeneration, and it is the accumulation of neurodegeneration that underlies increasing neurological disability in progressive MS. Determining pathological mechanisms at play in MS grey matter is therefore a key to our understanding of disease progression. We analysed complement expression and activation by immunocytochemistry and in situ hybridisation in frozen or formalin-fixed paraffin-embedded post-mortem tissue blocks from 22 progressive MS cases and made comparisons to inflammatory central nervous system disease and non-neurological disease controls. Expression of the transcript for C1qA was noted in neurons and the activation fragment and opsonin C3b-labelled neurons and glia in the MS cortical and deep grey matter. The density of immunostained cells positive for the classical complement pathway protein C1q and the alternative complement pathway activation fragment Bb was significantly increased in cortical grey matter lesions in comparison to control grey matter. The number of cells immunostained for the membrane attack complex was elevated in cortical lesions, indicating complement activation to completion. The numbers of classical (C1-inhibitor) and alternative (factor H) pathway regulator-positive cells were unchanged between MS and controls, whilst complement anaphylatoxin receptor-bearing microglia in the MS cortex were found closely apposed to cortical neurons. Complement immunopositive neurons displayed an altered nuclear morphology, indicative of cell stress/damage, supporting our finding of significant neurodegeneration in cortical grey matter lesions. Complement is activated in the MS cortical grey matter lesions in areas of elevated numbers of complement receptor-positive microglia and suggests that complement over-activation may contribute to the worsening pathology that underlies the

DMPD: Complement-mediated phagocytosis--the role of Syk. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 16754322 Complement-mediated phagocytosis--the role of Syk. Tohyama Y, Yamamura H. ...IUBMB Life. 2006 May-Jun;58(5-6):304-8. (.png) (.svg) (.html) (.csml) Show Complement-mediated phagocytosis-...-the role of Syk. PubmedID 16754322 Title Complement-mediated phagocytosis--the role of Syk. Authors Tohyama

Design of reactive power procurement in deregulated electricity market

African Journals Online (AJOL)

Reactive power management is different in the deregulated electricity market of various countries. In this paper, a novel reactive power procurement model is proposed, which ensure secure and reliable operation of deregulated electricity market. Various issues of reactive power management in the deregulated electricity ...

Deregulated power prices: comparison of diurnal patterns

International Nuclear Information System (INIS)

Ying Li; Flynn, P.C.

2004-01-01

We examine electrical power price, and in particular its daily and average weekday vs. weekend pattern of change, for 14 deregulated markets. Power price in deregulated markets shows fundamentally different patterns. North American markets show a monotonic diurnal weekday price pattern, while all other markets studied show more than one price peak. Deregulated power markets differ in maximum vs. minimum daily average price and in average weekday to weekend price, in turn creating a different incentive for a consumer to time shift power consuming activities. Markets differ in the extent to which a small fraction of the days shapes the average diurnal pattern and value of price. Deregulated markets show a wide variation in the correlation between load and price. Some deregulated markets, most notably Britain and Spain, show patterns that are predictable and consistent, and hence that can encourage a customer to shape consumption behaviors. Other markets, for example South Australia, have patterns that are inconsistent and irregular, and hence are hard for a customer to interpret; a customer in such a market will have a higher incentive to escape risk through hedging mechanisms. (Author)

Deregulated power prices: comparison of diurnal patterns

International Nuclear Information System (INIS)

Li Ying; Flynn, Peter C.

2004-01-01

We examine electrical power price, and in particular its daily and average weekday vs. weekend pattern of change, for 14 deregulated markets. Power price in deregulated markets shows fundamentally different patterns. North American markets show a monotonic diurnal weekday price pattern, while all other markets studied show more than one price peak. Deregulated power markets differ in maximum vs. minimum daily average price and in average weekday to weekend price, in turn creating a different incentive for a consumer to time shift power consuming activities. Markets differ in the extent to which a small fraction of the days shapes the average diurnal pattern and value of price. Deregulated markets show a wide variation in the correlation between load and price. Some deregulated markets, most notably Britain and Spain, show patterns that are predictable and consistent, and hence that can encourage a customer to shape consumption behaviors. Other markets, for example South Australia, have patterns that are inconsistent and irregular, and hence are hard for a customer to interpret; a customer in such a market will have a higher incentive to escape risk through hedging mechanisms

Hepatitis C virus NS3/4A protease inhibits complement activation by cleaving complement component 4.

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Seiichi Mawatari

Full Text Available BACKGROUND: It has been hypothesized that persistent hepatitis C virus (HCV infection is mediated in part by viral proteins that abrogate the host immune response, including the complement system, but the precise mechanisms are not well understood. We investigated whether HCV proteins are involved in the fragmentation of complement component 4 (C4, composed of subunits C4α, C4β, and C4γ, and the role of HCV proteins in complement activation. METHODS: Human C4 was incubated with HCV nonstructural (NS 3/4A protease, core, or NS5. Samples were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and then subjected to peptide sequencing. The activity of the classical complement pathway was examined using an erythrocyte hemolysis assay. The cleavage pattern of C4 in NS3/4A-expressing and HCV-infected cells, respectively, was also examined. RESULTS: HCV NS3/4A protease cleaved C4γ in a concentration-dependent manner, but viral core and NS5 did not. A specific inhibitor of NS3/4A protease reduced C4γ cleavage. NS3/4A protease-mediated cleavage of C4 inhibited classical pathway activation, which was abrogated by a NS3/4A protease inhibitor. In addition, co-transfection of cells with C4 and wild-type NS3/4A, but not a catalytic-site mutant of NS3/4A, produced cleaved C4γ fragments. Such C4 processing, with a concomitant reduction in levels of full-length C4γ, was also observed in HCV-infected cells expressing C4. CONCLUSIONS: C4 is a novel cellular substrate of the HCV NS3/4A protease. Understanding disturbances in the complement system mediated by NS3/4A protease may provide new insights into the mechanisms underlying persistent HCV infection.

Interpain A, a cysteine proteinase from Prevotella intermedia, inhibits complement by degrading complement factor C3.

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Michal Potempa

2009-02-01

Full Text Available Periodontitis is an inflammatory disease of the supporting structures of the teeth caused by, among other pathogens, Prevotella intermedia. Many strains of P. intermedia are resistant to killing by the human complement system, which is present at up to 70% of serum concentration in gingival crevicular fluid. Incubation of human serum with recombinant cysteine protease of P. intermedia (interpain A resulted in a drastic decrease in bactericidal activity of the serum. Furthermore, a clinical strain 59 expressing interpain A was more serum-resistant than another clinical strain 57, which did not express interpain A, as determined by Western blotting. Moreover, in the presence of the cysteine protease inhibitor E64, the killing of strain 59 by human serum was enhanced. Importantly, we found that the majority of P. intermedia strains isolated from chronic and aggressive periodontitis carry and express the interpain A gene. The protective effect of interpain A against serum bactericidal activity was found to be attributable to its ability to inhibit all three complement pathways through the efficient degradation of the alpha-chain of C3 -- the major complement factor common to all three pathways. P. intermedia has been known to co-aggregate with P. gingivalis, which produce gingipains to efficiently degrade complement factors. Here, interpain A was found to have a synergistic effect with gingipains on complement degradation. In addition, interpain A was able to activate the C1 complex in serum, causing deposition of C1q on inert and bacterial surfaces, which may be important at initial stages of infection when local inflammatory reaction may be beneficial for a pathogen. Taken together, the newly characterized interpain A proteinase appears to be an important virulence factor of P. intermedia.

Cartography of Pathway Signal Perturbations Identifies Distinct Molecular Pathomechanisms in Malignant and Chronic Lung Diseases

Science.gov (United States)

Arakelyan, Arsen; Nersisyan, Lilit; Petrek, Martin; Löffler-Wirth, Henry; Binder, Hans

2016-01-01

Lung diseases are described by a wide variety of developmental mechanisms and clinical manifestations. Accurate classification and diagnosis of lung diseases are the bases for development of effective treatments. While extensive studies are conducted toward characterization of various lung diseases at molecular level, no systematic approach has been developed so far. Here we have applied a methodology for pathway-centered mining of high throughput gene expression data to describe a wide range of lung diseases in the light of shared and specific pathway activity profiles. We have applied an algorithm combining a Pathway Signal Flow (PSF) algorithm for estimation of pathway activity deregulation states in lung diseases and malignancies, and a Self Organizing Maps algorithm for classification and clustering of the pathway activity profiles. The analysis results allowed clearly distinguish between cancer and non-cancer lung diseases. Lung cancers were characterized by pathways implicated in cell proliferation, metabolism, while non-malignant lung diseases were characterized by deregulations in pathways involved in immune/inflammatory response and fibrotic tissue remodeling. In contrast to lung malignancies, chronic lung diseases had relatively heterogeneous pathway deregulation profiles. We identified three groups of interstitial lung diseases and showed that the development of characteristic pathological processes, such as fibrosis, can be initiated by deregulations in different signaling pathways. In conclusion, this paper describes the pathobiology of lung diseases from systems viewpoint using pathway centered high-dimensional data mining approach. Our results contribute largely to current understanding of pathological events in lung cancers and non-malignant lung diseases. Moreover, this paper provides new insight into molecular mechanisms of a number of interstitial lung diseases that have been studied to a lesser extent. PMID:27200087

Economic and Environmental Effects of Airline Deregulation

NARCIS (Netherlands)

Schipper, Youdi; Rietveld, Piet

1997-01-01

This paper deals with the issue of regulatory reform in the airline industry, in connection with environmental externalities. Deregulation has led to shorter routes, higher frequencies, probably larger aircraft sizes and more intense peak traffic at airports. In addition, deregulation has led to

Specificity of EIA immunoassay for complement factor Bb testing.

Science.gov (United States)

Pavlov, Igor Y; De Forest, Nikol; Delgado, Julio C

2011-01-01

During the alternative complement pathway activation, factor B is cleaved in two fragments, Ba and Bb. Concentration of those fragments is about 2 logs lower than of factor B present in the blood, which makes fragment detection challenging because of potential cross-reactivity. Lack of information on Bb assay cross-reactivity stimulated the authors to investigate this issue. We ran 109 healthy donor EDTA plasmas and 80 sera samples with both factor B immunodiffusion (The Binding Site) and Quidel Bb EIA assays. During the study it was shown that physiological concentrations of gently purified factor B demonstrated approximately 0.15% cross-reactivity in the Quidel Bb EIA assay. We also observed that Bb concentration in serum is higher than in plasma due to complement activation during clot formation which let us use sera as samples representing complement activated state. Our study demonstrated that despite the potential 0.15% cross-reactivity between endogenous factor B and cleaved Bb molecule, measuring plasma concentrations of factor Bb is adequate to evaluate the activation of the alternative complement pathway.

Deregulation of S-adenosylmethionine biosynthesis and regeneration improves methylation in the E. coli de novo vanillin biosynthesis pathway.

Science.gov (United States)

Kunjapur, Aditya M; Hyun, Jason C; Prather, Kristala L J

2016-04-11

Vanillin is an industrially valuable molecule that can be produced from simple carbon sources in engineered microorganisms such as Saccharomyces cerevisiae and Escherichia coli. In E. coli, de novo production of vanillin was demonstrated previously as a proof of concept. In this study, a series of data-driven experiments were performed in order to better understand limitations associated with biosynthesis of vanillate, which is the immediate precursor to vanillin. Time-course experiments monitoring production of heterologous metabolites in the E. coli de novo vanillin pathway revealed a bottleneck in conversion of protocatechuate to vanillate. Perturbations in central metabolism intended to increase flux into the heterologous pathway increased average vanillate titers from 132 to 205 mg/L, but protocatechuate remained the dominant heterologous product on a molar basis. SDS-PAGE, in vitro activity measurements, and L-methionine supplementation experiments suggested that the decline in conversion rate was influenced more by limited availability of the co-substrate S-adenosyl-L-methionine (AdoMet or SAM) than by loss of activity of the heterologous O-methyltransferase. The combination of metJ deletion and overexpression of feedback-resistant variants of metA and cysE, which encode enzymes involved in SAM biosynthesis, increased average de novo vanillate titers by an additional 33% (from 205 to 272 mg/L). An orthogonal strategy intended to improve SAM regeneration through overexpression of native mtn and luxS genes resulted in a 25% increase in average de novo vanillate titers (from 205 to 256 mg/L). Vanillate production improved further upon supplementation with methionine (as high as 419 ± 58 mg/L), suggesting potential for additional enhancement by increasing SAM availability. Results from this study demonstrate context dependency of engineered pathways and highlight the limited methylation capacity of E. coli. Unlike in previous efforts to improve SAM or

Complement-Mediated Enhancement of Monocyte Adhesion to Endothelial Cells by HLA Antibodies, and Blockade by a Specific Inhibitor of the Classical Complement Cascade, TNT003

Science.gov (United States)

Valenzuela, Nicole M.; Thomas, Kimberly A.; Mulder, Arend; Parry, Graham C.; Panicker, Sandip; Reed, Elaine F.

2017-01-01

Background Antibody-mediated rejection (AMR) of most solid organs is characterized by evidence of complement activation and/or intragraft macrophages (C4d + and CD68+ biopsies). We previously demonstrated that crosslinking of HLA I by antibodies triggered endothelial activation and monocyte adhesion. We hypothesized that activation of the classical complement pathway at the endothelial cell surface by HLA antibodies would enhance monocyte adhesion through soluble split product generation, in parallel with direct endothelial activation downstream of HLA signaling. Methods Primary human aortic endothelial cells (HAEC) were stimulated with HLA class I antibodies in the presence of intact human serum complement. C3a and C5a generation, endothelial P-selectin expression, and adhesion of human primary and immortalized monocytes (Mono Mac 6) were measured. Alternatively, HAEC or monocytes were directly stimulated with purified C3a or C5a. Classical complement activation was inhibited by pretreatment of complement with an anti-C1s antibody (TNT003). Results Treatment of HAEC with HLA antibody and human complement increased the formation of C3a and C5a. Monocyte recruitment by human HLA antibodies was enhanced in the presence of intact human serum complement or purified C3a or C5a. Specific inhibition of the classical complement pathway using TNT003 or C1q-depleted serum significantly reduced adhesion of monocytes in the presence of human complement. Conclusions Despite persistent endothelial viability in the presence of HLA antibodies and complement, upstream complement anaphylatoxin production exacerbates endothelial exocytosis and leukocyte recruitment. Upstream inhibition of classical complement may be therapeutic to dampen mononuclear cell recruitment and endothelial activation characteristic of microvascular inflammation during AMR. PMID:28640789

Protective function of complement against alcohol-induced rat liver damage.

Science.gov (United States)

Bykov, Igor L; Väkevä, Antti; Järveläinen, Harri A; Meri, Seppo; Lindros, Kai O

2004-11-01

The complement system can promote tissue damage or play a homeostatic role in the clearance and disposal of damaged tissue. We assessed the role of the terminal complement pathway in alcohol-induced liver damage in complement C6 (C6-/-) genetically deficient rats. C6-/- and corresponding C6+/+ rats were continuously exposed to ethanol by feeding ethanol-supplemented liquid diet for six weeks. Liver samples were analyzed for histopathology and complement component deposition by immunofluorescence microscopy. Prostaglandin E receptors and cytokine mRNA levels were analyzed by RT-PCR and plasma cytokines by ELISA. Deposition of complement components C1, C3, C8 and C9 was observed in C6+/+ rats, but not in C6-/- animals. The histopathological changes, the liver weight increase and the elevation of the plasma pro-/anti-inflammatory TNF-alpha/IL-10 ratio were, on the other hand, more marked in C6-/- rats. Furthermore, ethanol enhanced the hepatic mRNA expression of the prostaglandin E receptors EP2R and EP4R exclusively in the C6-/- rats. Our results indicate that a deficient terminal complement pathway predisposes to tissue injury and promotes a pro-inflammatory cytokine response. This suggests that an intact complement system has a protective function in the development of alcoholic liver damage.

Power Buying: Planning For Your Deregulated Future.

Science.gov (United States)

Robertson, Wayne K.

1997-01-01

Colleges and universities can benefit from the coming deregulation of utilities. Deregulation creates opportunity for facility managers to aggressively negotiate agreements, implement changes to the physical plant to make the institution a more attractive customer, and explore new, less expensive energy supply options and alternatives. Some action…

Complement in the Initiation and Evolution of Rheumatoid Arthritis

Science.gov (United States)

Holers, V. Michael; Banda, Nirmal K.

2018-01-01

The complement system is a major component of the immune system and plays a central role in many protective immune processes, including circulating immune complex processing and clearance, recognition of foreign antigens, modulation of humoral and cellular immunity, removal of apoptotic and dead cells, and engagement of injury resolving and tissue regeneration processes. In stark contrast to these beneficial roles, however, inadequately controlled complement activation underlies the pathogenesis of human inflammatory and autoimmune diseases, including rheumatoid arthritis (RA) where the cartilage, bone, and synovium are targeted. Recent studies of this disease have demonstrated that the autoimmune response evolves over time in an asymptomatic preclinical phase that is associated with mucosal inflammation. Notably, experimental models of this disease have demonstrated that each of the three major complement activation pathways plays an important role in recognition of injured joint tissue, although the lectin and amplification pathways exhibit particularly impactful roles in the initiation and amplification of damage. Herein, we review the complement system and focus on its multi-factorial role in human patients with RA and experimental murine models. This understanding will be important to the successful integration of the emerging complement therapeutics pipeline into clinical care for patients with RA. PMID:29892280

Consequences of electricity deregulation on nuclear safety

International Nuclear Information System (INIS)

Podjavorsek, M.

2007-01-01

The evolution of deregulation of electricity market started a couple of years ago and has not been finished yet. Deregulation causes increased pressure to reduce the costs of electricity generation. This presents a new challenge to regulatory bodies. They have to assess the impact of these changes on the safety of nuclear power plants. Accordingly, it is important to identify the risks to the nuclear power industry resulting from the deregulation. Today's trend is that the number of electricity generating power companies will be reduced in Europe and also in Slovenia due to tough competition in the electricity market. The electricity price has decreased after the introduction of the deregulated market in most countries. This has been also the main reason for less investment to new generating capacities since the price has been lower than the generation costs. Investment problems are also present for the existing units, because of danger of inappropriate maintenance and reduction of the number of staff and their qualifications below the desired level that leads to loss of institutional memory. It is expected that only the biggest companies can stand the consequences of competition in electricity prices and consequential pressure to reduce the cost. In order to review the impact of deregulation of the electricity market some relevant points are discussed in this paper such as the need to cut costs of companies by reducing the number of their activities and increasing the efficiency in the remaining activities and /or outsourcing of activities, power station operating regime, safety culture, grid reliability, reliability and safety of operation, increased number of transients, ageing of components, outage duration, extended cycle and response of nuclear regulators. From a regulatory point of view the impact of deregulation on nuclear safety is an important issue. This paper also discusses analyses and evaluations of this impact and proposes some measures how to

Regulating deregulated energy markets

International Nuclear Information System (INIS)

Jackson, M.

2002-01-01

The North American gas and electricity markets are fast evolving, and regulators are currently faced with a host of issues such as market-based rates, unbundling, stranded costs, open access, and incentive regulation are surfacing as a result of deregulation. The regulatory environment in Ontario was reviewed by the author. Deregulated markets rule, from commodities to gas and electricity. Additionally, there is an evolution of traditional utility regulation. A look at deregulated markets revealed that there are regulations on boundary conditions on the deregulated market. Under the Ontario Energy Board (OEB), all generators, transmitters, distributors, and retailers of electricity must be licensed. The standard supply service (SSS) offered by electricity distributors and system gas which is still being sold by natural gas distributors continues to be regulated by OEB. One issue that was addressed was separation for revenues and costs of the utility's purchase and sale of gas business, at least for accounting purposes. The next issue discussed was cost of system gas and SSS, followed by timely signals and prudent incurred costs. Historical benefits were reviewed, such as historical commitments to low-cost electricity. Pooling transportation costs, transmission pricing continued, market-based rates, unbundling, stranded costs, open access, incentive regulation/ performance based regulation (PBR) were all discussed. Price cap on PBR, both partial and comprehensive were looked at. A requirement to review guidelines on cost of capital and an application to extend blanket approval provisions for gas storage were discussed, as they are amongst some of the challenges of the future. Other challenges include revised rules and practice and procedure; practice directions for cost awards, appeals, and other functions; confidentiality guidelines; and refinements to the role of and approaches to alternative dispute resolution. The future role of regulators was examined in light

Regulatory trends : deregulation, where in the world is it working?

International Nuclear Information System (INIS)

Sofield, J.

2001-01-01

The issue of electricity deregulation was the focus of this Power-Point presentation, which discussed what deregulation entails, what it is meant to achieve and whether there is only one right answer. Different approaches and performance results were presented with reference to international experiences in the United Kingdom, Australia, New Zealand, and California. The main objective of deregulation is introduce competition to give customers a choice between suppliers and products, to allow market forces to set prices with the hope that they will be lower, and to encourage industry efficiency, reduce costs, improve productivity, and ensure that the right investments are made. The underlying agenda is to raise billions of dollars to reduce government debt and to transfer the risks and investment requirements to the investors and away from the government/taxpayers and ratepayers. Deregulation entails restructuring, privatization and unbundling of monopolies. It also entails a set of market rules and new systems processes to enable retail competition. The author emphasized that there are different characteristics to deregulation in each jurisdiction and that the state of the pre-deregulation industry plays a significant role in the eventual success of deregulation. The lessons learned from international experience is that open, non-discriminatory access is essential for both transmission and distribution and that political will for restructuring is essential. It was also determined that partial deregulation will not work, since wholesale and retail markets are connected. It was concluded that deregulation can work to different degrees under different designs. Progress so far has been slow and customers have yet to see the full benefits of deregulation. tabs

Energy deregulation: the Vattenfall experience

International Nuclear Information System (INIS)

Nyquist, C.E.

1999-01-01

In 1992, Sweden prepared itself for deregulation by transforming Vattenfall, the country's main supplier of energy, from a public utility into a limited liability company. Vattenfall was still 100% owned by the state, but began to operate as a commercial entity with a separate board of directors. On January 1, 1996, Sweden and Finland deregulated, and the three Nordic countries - Norway, Sweden and Denmark - became a completely open market. Beginning November 1, 1999, Sweden will introduce simplified metering, bringing competition directly to consumers, which represents the purest and most advanced form of electricity competition, forcing Vattenfall and its peers to fight for the loyalty of customers from the smallest retail household upwards. As a central participant in deregulation, Vattenfall was faced with some major challenges. In essence, Vattenfall had to evolve from a parochial Swedish public utility into a pan-European energy services company. The transition was successful and Vattenfall today represents about 20% of Scandinavia's generation capacity, with operations that are about 1/2 the size of those of Ontario Hydro. Vattenfall had to take a number of steps to get ready for a fully competitive retail market. First it established a market oriented group organization based on three units: Vattenfall Electricity Generation, Vattenfall Energy Market, and Vattenfall Electricity Networks and Services. Second it expanded its relationship with its customers. Third it adjusted to the fact that electricity deregulation led to an immediate generation surplus. The main lessons learned from the experience are summarized

Functional analysis of Ficolin-3 mediated complement activation

DEFF Research Database (Denmark)

Hein, Estrid; Honoré, Christian; Skjoedt, Mikkel-Ole

2010-01-01

Ficolin-3 mediated complement activation that could be applicable for research and clinical use. Bovine serum albumin (BSA) was acetylated (acBSA) and chosen as a solid phase ligand for Ficolins in microtiter wells. Binding of Ficolins on acBSA was evaluated, as was functional complement activation...... was applied to the samples that inhibited interference from the classical pathway due to the presence of anti-BSA antibodies in some sera. We describe a novel functional method for measuring complement activation mediated by Ficolin-3 in human serum up to the formation of TCC. The assay provides...

Complement Activation by Ceramide Transporter Proteins

NARCIS (Netherlands)

Bode, G.H.; Losen, M.; Buurman, W.A.; Veerhuis, R.; Molenaar, P.C.; Steinbusch, H.W.M.; De Baets, M.H.; Daha, MR; Martinez-Martinez, P.

2014-01-01

C1q is the initiator of the classical complement pathway and, as such, is essential for efficient opsonization and clearance of pathogens, altered self-structures, and apoptotic cells. The ceramide transporter protein (CERT) and its longer splicing isoform CERTL are known to interact with

Complement pathway biomarkers and age-related macular degeneration

Science.gov (United States)

Gemenetzi, M; Lotery, A J

2016-01-01

In the age-related macular degeneration (AMD) ‘inflammation model', local inflammation plus complement activation contributes to the pathogenesis and progression of the disease. Multiple genetic associations have now been established correlating the risk of development or progression of AMD. Stratifying patients by their AMD genetic profile may facilitate future AMD therapeutic trials resulting in meaningful clinical trial end points with smaller sample sizes and study duration. PMID:26493033

Deregulation - a source of crisis?

International Nuclear Information System (INIS)

Haavardstein, Hilde; Sandsmark, Maria

2003-01-01

Since the beginning of the 1990s, deregulation has become widespread in many of the worlds power markets. When it is no longer the authorities, but the players in the market who are deciding on investments in new production capacity, on the basis of business economic estimates of profitability, it is important that the external conditions are worked out such that they provide incentives to investments of the right extent and to the right time. Examples from deregulated markets show that the formulation of such external frames has contributed to a tight power balance

Banking deregulation and corporate tax avoidance

Directory of Open Access Journals (Sweden)

Bill B. Francis

2017-06-01

Full Text Available We investigate whether tax avoidance substitutes for external financing. We exploit interstate banking deregulation as a quasi-external shock to examine whether firms engage in less tax avoidance after banking deregulation, because of cheaper and easier access to credit from banks. We find no empirical evidence to support this substitutive relation, even for firms with higher financial constraints or firms with higher external financing dependence.

Human pentraxin 3 binds to the complement regulator c4b-binding protein.

Directory of Open Access Journals (Sweden)

Anne Braunschweig

Full Text Available The long pentraxin 3 (PTX3 is a soluble recognition molecule with multiple functions including innate immune defense against certain microbes and the clearance of apoptotic cells. PTX3 interacts with recognition molecules of the classical and lectin complement pathways and thus initiates complement activation. In addition, binding of PTX3 to the alternative complement pathway regulator factor H was shown. Here, we show that PTX3 binds to the classical and lectin pathway regulator C4b-binding protein (C4BP. A PTX3-binding site was identified within short consensus repeats 1-3 of the C4BP α-chain. PTX3 did not interfere with the cofactor activity of C4BP in the fluid phase and C4BP maintained its complement regulatory activity when bound to PTX3 on surfaces. While C4BP and factor H did not compete for PTX3 binding, the interaction of C4BP with PTX3 was inhibited by C1q and by L-ficolin. PTX3 bound to human fibroblast- and endothelial cell-derived extracellular matrices and recruited functionally active C4BP to these surfaces. Whereas PTX3 enhanced the activation of the classical/lectin pathway and caused enhanced C3 deposition on extracellular matrix, deposition of terminal pathway components and the generation of the inflammatory mediator C5a were not increased. Furthermore, PTX3 enhanced the binding of C4BP to late apoptotic cells, which resulted in an increased rate of inactivation of cell surface bound C4b and a reduction in the deposition of C5b-9. Thus, in addition to complement activators, PTX3 interacts with complement inhibitors including C4BP. This balanced interaction on extracellular matrix and on apoptotic cells may prevent excessive local complement activation that would otherwise lead to inflammation and host tissue damage.

Deregulation of the ubiquitin-proteasome system is the predominant molecular pathology in OPMD animal models and patients

DEFF Research Database (Denmark)

Anvar, Seyed Yahya; hoen, Peter Ac; Venema, Andrea

2011-01-01

Oculopharyngeal muscular dystrophy (OPMD) is a late-onset progressive muscle disorder caused by a poly-alanine expansion mutation in the Poly(A) Binding Protein Nuclear 1 (PABPN1). The molecular mechanisms that regulate disease onset and progression are largely unknown. In order to identify...... molecular pathways that are consistently associated with OPMD, we performed an integrated high-throughput transcriptome study in affected muscles of OPMD animal models and patients. The ubiquitin-proteasome system (UPS) was found to be the most consistently and significantly OPMD-deregulated pathway across...

Deposition of mannose-binding lectin and ficolins and activation of the lectin pathway of complement on the surface of polyurethane tubing used for cardiopulmonary bypass.

Science.gov (United States)

Eppa, Łukasz; Pągowska-Klimek, Izabela; Świerzko, Anna S; Moll, Maciej; Krajewski, Wojciech R; Cedzyński, Maciej

2018-04-01

The artificial surface used for cardiopulmonary bypass (CPB) is a crucial factor activating the complement system and thus contributing to the generation of a systemic inflammatory response. The activation of classical and alternative pathways on this artificial surface is well known. In contrast, lectin pathway (LP) activation has not been fully investigated, although noted during CPB in several studies. Moreover, we have recently proved the contribution of the LP to the generation of the systemic inflammatory response syndrome after pediatric cardiac surgery. The aim of this study was to assess LP-mediated complement activation on the surface of polyurethane CPB circuit tubing (noncoated Chalice ® ), used for CPB procedures in children with congenital heart disease. We found deposition of mannose-binding lectin, ficolin-1, -2, and -3 on the surface of unused tubing and on tubing used for CPB from a small minority of patients. Furthermore, we observed deposition of complement C4 activation products on tubing used for CPB and previously unused tubing after incubation with normal serum. The latter finding indicates LP activation in vitro on the polyurethane surface. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1202-1208, 2018. © 2017 Wiley Periodicals, Inc.

Complement activation by ceramide transporter proteins.

Science.gov (United States)

Bode, Gerard H; Losen, Mario; Buurman, Wim A; Veerhuis, Robert; Molenaar, Peter C; Steinbusch, Harry W M; De Baets, Marc H; Daha, Mohamed R; Martinez-Martinez, Pilar

2014-02-01

C1q is the initiator of the classical complement pathway and, as such, is essential for efficient opsonization and clearance of pathogens, altered self-structures, and apoptotic cells. The ceramide transporter protein (CERT) and its longer splicing isoform CERTL are known to interact with extracellular matrix components, such as type IV collagen, and with the innate immune protein serum amyloid P. In this article, we report a novel function of CERT in the innate immune response. Both CERT isoforms, when immobilized, were found to bind the globular head region of C1q and to initiate the classical complement pathway, leading to activation of C4 and C3, as well as generation of the membrane attack complex C5b-9. In addition, C1q was shown to bind to endogenous CERTL on the surface of apoptotic cells. These results demonstrate the role of CERTs in innate immunity, especially in the clearance of apoptotic cells.

Potential of Murine IgG1 and Human IgG4 to Inhibit the Classical Complement and Fcγ Receptor Activation Pathways

Directory of Open Access Journals (Sweden)

Gina-Maria Lilienthal

2018-05-01

Full Text Available IgG antibodies (Abs mediate their effector functions through the interaction with Fcγ receptors (FcγRs and the complement factors. The main IgG-mediated complement activation pathway is induced through the binding of complement C1q to IgG Abs. This interaction is dependent on antigen-dependent hexamer formation of human IgG1 and IgG3 to increase the affinity for the six-headed C1q molecule. By contrast, human IgG4 fails to bind to C1q. Instead, it has been suggested that human IgG4 can block IgG1 and IgG3 hexamerization required for their binding to C1q and activating the complement. Here, we show that murine IgG1, which functionally resembles human IgG4 by not interacting with C1q, inhibits the binding of IgG2a, IgG2b, and IgG3 to C1q in vitro, and suppresses IgG2a-mediated complement activation in a hemolytic assay in an antigen-dependent and IgG subclass-specific manner. From this perspective, we discuss the potential of murine IgG1 and human IgG4 to block the complement activation as well as suppressive effects of sialylated IgG subclass Abs on FcγR-mediated immune cell activation. Accumulating evidence suggests that both mechanisms seem to be responsible for preventing uncontrolled IgG (autoAb-induced inflammation in mice and humans. Distinct IgG subclass distributions and functionally opposite IgG Fc glycosylation patterns might explain different outcomes of IgG-mediated immune responses and provide new therapeutic options through the induction, enrichment, or application of antigen-specific sialylated human IgG4 to prevent complement and FcγR activation as well.

Energy and the deregulated marketplace 1998 survey

International Nuclear Information System (INIS)

Fowler, R.B.

1999-01-01

In this comprehensive survey of the energy and deregulated marketplace, 911 respondents indicate how deregulation will impact their business. Well organized for easy reference this published survey report provides answers on how companies will procure electricity and natural gas, and what criteria will be used in their decision process. The results presented also illustrate effect of real time pricing on the procurement of energy equipment. Readers will be able to see whether companies are delaying the purchase of energy efficiency equipment as a result of deregulation, as well as what current trends are developing in the use of energy services and performance contracting. The performance and overall cost effectiveness of various types of energy efficient equipment is also rated by respondents, and the results of existing installations is reported. Responses are broken down and can be assessed by respondent categories, including utility, energy supplier, energy user, power marketer, ESCO, equipment supplier, and consultant. This survey report offers a valuable tool for all companies whose business and marketing strategies are impacted by deregulation

Electricity deregulation - impact on gas users and markets

International Nuclear Information System (INIS)

Koeppel, H.

1995-01-01

Various scenarios for the natural gas market as a function a electricity deregulation were predicted. One scenario was the formation of an integrated market where sellers would offer a broad spectrum of energy products. This diversification would expand into the retail sector across North America. The second effect of electricity deregulation was energy cost reduction. The consumers have already been experiencing this benefit of deregulation. Cost reduction has also stimulated competition among energy suppliers, and improved suppliers' response to consumers'demands. The eventual shake-out of energy suppliers was predicted. Smaller companies that could not survive the competition would give up the market to larger companies that understood and met the customers' needs. It was concluded that deregulation of the electricity industry would have an enormous impact on the natural gas industry and that there would be opportunities for gain among buyers and sellers

Telecommunications Deregulation

OpenAIRE

Jerry A. Hausman; William E. Taylor

2012-01-01

From Fred Kahn's writings and experiences as a telecommunications regulator and commenter, we draw the following conclusions: prices must be informed by costs; costs are actual incremental costs; costs and prices are an outcome of a Schumpeterian competitive process, not the starting point; excluding incumbents from markets is fundamentally anticompetitive; and a regulatory transition to deregulation entails propensities to micromanage the process to generate preferred outcomes, visible compe...

Internet-based wide area measurement applications in deregulated power systems

Science.gov (United States)

Khatib, Abdel-Rahman Amin

Since the deregulation of power systems was started in 1989 in the UK, many countries have been motivated to undergo deregulation. The United State started deregulation in the energy sector in California back in 1996. Since that time many other states have also started the deregulation procedures in different utilities. Most of the deregulation market in the United States now is in the wholesale market area, however, the retail market is still undergoing changes. Deregulation has many impacts on power system network operation and control. The number of power transactions among the utilities has increased and many Independent Power Producers (IPPs) now have a rich market for competition especially in the green power market. The Federal Energy Regulatory Commission (FERC) called upon utilities to develop the Regional Transmission Organization (RTO). The RTO is a step toward the national transmission grid. RTO is an independent entity that will operate the transmission system in a large region. The main goal of forming RTOs is to increase the operation efficiency of the power network under the impact of the deregulated market. The objective of this work is to study Internet based Wide Area Information Sharing (WAIS) applications in the deregulated power system. The study is the first step toward building a national transmission grid picture using information sharing among utilities. Two main topics are covered as applications for the WAIS in the deregulated power system, state estimation and Total Transfer Capability (TTC) calculations. As a first step for building this national transmission grid picture, WAIS and the level of information sharing of the state estimation calculations have been discussed. WAIS impacts to the TTC calculations are also covered. A new technique to update the TTC using on line measurements based on WAIS created by sharing state estimation is presented.

Implications of U.S. electricity deregulation

International Nuclear Information System (INIS)

Gottfried, D.A.

1997-01-01

This article is a concise summary of the potential impacts of electric utility deregulation, including the resolution of stranded costs, impact on electricity rates, reformation of utilities, and reshuffling of the nation's fuel portfolio. The national and state implications of the deregulation of the electricity industry are monumental and overwhelming. The implications occur on many fronts, including monetary, quality, reliability, and environmental issues. Many significant changes will occur as a result--some will be positive and others may be more disturbing

Deregulator: Judgment Day for microeconomics

International Nuclear Information System (INIS)

Keen, S.

2004-01-01

The economic theory that motivated the deregulation and privatization of the US electricity industry is seriously flawed in three crucial ways. First, the Marshallian theory of the firm is based on two mathematical errors which, when amended, reverse the accepted welfare rankings of competitive and monopoly industry structures: on the grounds of corrected neoclassical theory, monopoly should be preferred to competition. Second, while proponents of deregulation expected market-clearing equilibrium prices to apply, it is well known that the equilibrium of a system of spot market prices is unstable. This implies that imposing spot market pricing on as basic an industry as electricity is likely to lead to the kind of volatility observed under the deregulation. Third, extensive empirical research has established that on the order of 95% of firms do not produce under conditions of rising marginal cost. Requiring electricity firms to price at marginal cost was therefore likely to lead to bankruptcies, as indeed occurred. The economic preference for marginal cost spot market pricing is therefore theoretically unsound, and it is no wonder that the actual deregulatory experience was as bad as it was. (author)

Deregulator: Judgment Day for microeconomics

Energy Technology Data Exchange (ETDEWEB)

Keen, S. [University of Western Sydney, Penrith (Australia). School of Economics and Finance

2004-09-01

The economic theory that motivated the deregulation and privatization of the US electricity industry is seriously flawed in three crucial ways. First, the Marshallian theory of the firm is based on two mathematical errors which, when amended, reverse the accepted welfare rankings of competitive and monopoly industry structures: on the grounds of corrected neoclassical theory, monopoly should be preferred to competition. Second, while proponents of deregulation expected market-clearing equilibrium prices to apply, it is well known that the equilibrium of a system of spot market prices is unstable. This implies that imposing spot market pricing on as basic an industry as electricity is likely to lead to the kind of volatility observed under the deregulation. Third, extensive empirical research has established that on the order of 95% of firms do not produce under conditions of rising marginal cost. Requiring electricity firms to price at marginal cost was therefore likely to lead to bankruptcies, as indeed occurred. The economic preference for marginal cost spot market pricing is therefore theoretically unsound, and it is no wonder that the actual deregulatory experience was as bad as it was. (author)

Overexpression of the riboflavin biosynthetic pathway in Pichia pastoris

Directory of Open Access Journals (Sweden)

Mattanovich Diethard

2008-07-01

Full Text Available Abstract Background High cell density cultures of Pichia pastoris grown on methanol tend to develop yellow colored supernatants, attributed to the release of free flavins. The potential of P. pastoris for flavin overproduction is therefore given, but not pronounced when the yeast is grown on glucose. The aim of this study is to characterize the relative regulatory impact of each riboflavin synthesis gene. Deeper insight into pathway control and the potential of deregulation is established by overexpression of the single genes as well as a combined deregulation of up to all six riboflavin synthesis genes. Results Overexpression of the first gene of the riboflavin biosynthetic pathway (RIB1 is already sufficient to obtain yellow colonies and the accumulation of riboflavin in the supernatant of shake flask cultures growing on glucose. Sequential deregulation of all the genes, by exchange of their native promoter with the strong and constitutive glyceraldehyde-3-phosphate dehydrogenase promoter (PGAP increases the riboflavin accumulation significantly. Conclusion The regulation of the pathway is distributed over more than one gene. High cell density cultivations of a P. pastoris strain overexpressing all six RIB genes allow the accumulation of 175 mg/L riboflavin in the supernatant. The basis for rational engineering of riboflavin production in P. pastoris has thus been established.

Ouabain rescues rat nephrogenesis during intrauterine growth restriction by regulating the complement and coagulation cascades and calcium signaling pathway.

Science.gov (United States)

Chen, L; Yue, J; Han, X; Li, J; Hu, Y

2016-02-01

Intrauterine growth restriction (IUGR) is associated with a reduction in the numbers of nephrons in neonates, which increases the risk of hypertension. Our previous study showed that ouabain protects the development of the embryonic kidney during IUGR. To explore this molecular mechanism, IUGR rats were induced by protein and calorie restriction throughout pregnancy, and ouabain was delivered using a mini osmotic pump. RNA sequencing technology was used to identify the differentially expressed genes (DEGs) of the embryonic kidneys. DEGs were submitted to the Database for Annotation and Visualization and Integrated Discovery, and gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted. Maternal malnutrition significantly reduced fetal weight, but ouabain treatment had no significant effect on body weight. A total of 322 (177 upregulated and 145 downregulated) DEGs were detected between control and the IUGR group. Meanwhile, 318 DEGs were found to be differentially expressed (180 increased and 138 decreased) between the IUGR group and the ouabain-treated group. KEGG pathway analysis indicated that maternal undernutrition mainly disrupts the complement and coagulation cascades and the calcium signaling pathway, which could be protected by ouabain treatment. Taken together, these two biological pathways may play an important role in nephrogenesis, indicating potential novel therapeutic targets against the unfavorable effects of IUGR.

Exposure to endocrine disruptor induces transgenerational epigenetic deregulation of microRNAs in primordial germ cells.

Directory of Open Access Journals (Sweden)

Miguel A Brieño-Enríquez

Full Text Available In mammals, germ cell differentiation is initiated in the Primordial Germ Cells (PGCs during fetal development. Prenatal exposure to environmental toxicants such as endocrine disruptors may alter PGC differentiation, development of the male germline and induce transgenerational epigenetic disorders. The anti-androgenic compound vinclozolin represents a paradigmatic example of molecule causing transgenerational effects on germ cells. We performed prenatal exposure to vinclozolin in mice and analyzed the phenotypic and molecular changes in three successive generations. A reduction in the number of embryonic PGCs and increased rate of apoptotic cells along with decrease of fertility rate in adult males were observed in F1 to F3 generations. Blimp1 is a crucial regulator of PGC differentiation. We show that prenatal exposure to vinclozolin deregulates specific microRNAs in PGCs, such as miR-23b and miR-21, inducing disequilibrium in the Lin28/let-7/Blimp1 pathway in three successive generations of males. As determined by global maps of cytosine methylation, we found no evidence for prominent changes in DNA methylation in PGCs or mature sperm. Our data suggest that embryonic exposure to environmental endocrine disruptors induces transgenerational epigenetic deregulation of expression of microRNAs affecting key regulatory pathways of germ cells differentiation.

Deregulated power prices: comparison of volatility

International Nuclear Information System (INIS)

Li Ying; Flynn, P.C.

2004-01-01

We examine electrical power price variability for 14 deregulated markets. Power price volatility is measured by price velocity, the daily average of the absolute value of price change per hour. Deregulated markets show a wide variability in price velocity. Some price velocity is expected and arises from the daily diurnal price pattern, which differs significantly between markets. Even when the expected daily variability in price is removed, the residual unexpected variability differs between markets. Some deregulated markets, most notably Britain and Spain, show patterns that are predictable and consistent and have low values of unexpected price velocity. These markets create a climate conducive to consumers facing the market through real time pricing and shaping consumption behaviors in response to price changes. Other markets, for example, South Australia and Alberta, have patterns that are inconsistent and irregular, and hence are hard for a customer to interpret; a customer in such a market will have a higher incentive to avoid demand side management and escape risk through hedging mechanisms

Transmission planning in a deregulated environment

DEFF Research Database (Denmark)

Xu, Zhao

2006-01-01

The worldwide trend for the deregulation of the electricity generation and transmission industries has led to dramatic changes in system operation and planning procedures. The optimum approach to transmission-expansion planning in a deregulated environment is an open problem especially when the r...... electricity market grid are performed. In addition, the proposed method is compared with a traditional planning method to further verify its effectiveness....... the responsibilities of the organisations carrying out the planning work need to be addressed. To date there is a consensus that the system operator and network manager perform the expansion planning work in a centralised way. However, with an increasing input from the electricity market, the objectives, constraints...... and approaches toward transmission planning should be carefully designed to ensure system reliability as well as meeting the market requirements. A market-oriented approach for transmission planning in a deregulated environment is proposed. Case studies using the IEEE 14-bus system and the Australian national...

Complement: a key system for immune surveillance and homeostasis.

Science.gov (United States)

Ricklin, Daniel; Hajishengallis, George; Yang, Kun; Lambris, John D

2010-09-01

Nearly a century after the significance of the human complement system was recognized, we have come to realize that its functions extend far beyond the elimination of microbes. Complement acts as a rapid and efficient immune surveillance system that has distinct effects on healthy and altered host cells and foreign intruders. By eliminating cellular debris and infectious microbes, orchestrating immune responses and sending 'danger' signals, complement contributes substantially to homeostasis, but it can also take action against healthy cells if not properly controlled. This review describes our updated view of the function, structure and dynamics of the complement network, highlights its interconnection with immunity at large and with other endogenous pathways, and illustrates its multiple roles in homeostasis and disease.

Novel assays to assess the functional capacity of the classical, the alternative and the lectin pathways of the complement system

DEFF Research Database (Denmark)

Palarasah, Y; Nielsen, C; Sprogøe, U

2011-01-01

is therefore of great importance. In this study, we present novel improved enzyme-linked immunosorbent assays for the functional assessment of the three individual pathways of the complement system. The method is applicable at high serum concentrations and we demonstrate that it minimizes both false negative...... as well as false positive results. In particular, for the functional mannose-binding lectin activity it represents an improvement on the existing assays. In this respect, the present assays represent novel improved diagnostic protocols for patients with suspected immunodeficiencies related...

Deregulated WNT signaling in childhood T-cell acute lymphoblastic leukemia

International Nuclear Information System (INIS)

Ng, O H; Erbilgin, Y; Firtina, S; Celkan, T; Karakas, Z; Aydogan, G; Turkkan, E; Yildirmak, Y; Timur, C; Zengin, E; Dongen, J J M van; Staal, F J T; Ozbek, U; Sayitoglu, M

2014-01-01

WNT signaling has been implicated in the regulation of hematopoietic stem cells and plays an important role during T-cell development in thymus. Here we investigated WNT pathway activation in childhood T-cell acute lymphoblastic leukemia (T-ALL) patients. To evaluate the potential role of WNT signaling in T-cell leukomogenesis, we performed expression analysis of key components of WNT pathway. More than 85% of the childhood T-ALL patients showed upregulated β-catenin expression at the protein level compared with normal human thymocytes. The impact of this upregulation was reflected in high expression of known target genes (AXIN2, c-MYC, TCF1 and LEF). Especially AXIN2, the universal target gene of WNT pathway, was upregulated at both mRNA and protein levels in ∼40% of the patients. When β-CATENIN gene was silenced by small interfering RNA, the cancer cells showed higher rates of apoptosis. These results demonstrate that abnormal WNT signaling activation occurs in a significant fraction of human T-ALL cases independent of known T-ALL risk factors. We conclude that deregulated WNT signaling is a novel oncogenic event in childhood T-ALL

Genetically engineered fusion of MAP-1 and factor H domains 1-5 generates a potent dual upstream inhibitor of both the lectin and alternative complement pathways

DEFF Research Database (Denmark)

Nordmaj, Mie Anemone; Munthe-Fog, Lea; Hein, Estrid

2015-01-01

Inhibition of the complement cascade has emerged as an option for treatment of a range of diseases. Mannose-binding lectin/ficolin/collectin-associated protein (MAP-1) is a pattern recognition molecule (PRM)-associated inhibitor of the lectin pathway. The central regulator of the alternative......:4 in a solid-phase functional assay, only the first 5 N-terminal domains of complement FH fused to the C-terminal part of full-length MAP-1 chimeric construct were able to combine inhibition of lectin and AP activation with an half maximal inhibitory concentration of ∼ 100 and 20 nM, respectively. No effect...

Genetic Variation in Complement Component 2 of the Classical Complement Pathway is Associated with Increased Mortality and Infection: A Study of 627 Trauma Patients

Science.gov (United States)

Morris, John A.; Francois, Cedric; Olson, Paul K.; Cotton, Bryan A.; Summar, Marshall; Jenkins, Judith M.; Norris, Patrick R.; Moore, Jason H.; Williams, Anna E.; McNew, Brent S.; Canter, Jeffrey A.

2009-01-01

Trauma is a disease of inflammation. Complement Component 2 (C2) is a protease involved in activation of complement through the classical pathway and has been implicated in a variety of chronic inflammatory diseases. We hypothesized that genetic variation in C2 (E318D) identifies a high-risk subgroup of trauma patients reflecting increased mortality and infection (Ventilator associated pneumonia: VAP). Consequently, genetic variation in C2 may stratify patient risk and illuminate underlying mechanisms for therapeutic intervention. Methods DNA samples from 702 trauma patients were genotyped for C2 E318D and linked with covariates (age: mean 42.8 years, gender: 74% male, ethnicity: 80% Caucasian, mechanism: 84% blunt, ISS: mean 25.0, admission lactate: mean 3.13 mEq/L) and outcomes: mortality 9.9% and VAP: 18.5%. VAP was defined by quantitative bronchoalveolar lavage (>104). Multivariate regression determined the relationship of genotype and covariates to risk of death and VAP. However, patients with ISS ≥ 45 were excluded from the multivariate analysis, as magnitude of injury overwhelms genetics and covariates in determining outcome. Results 52 patients (8.3%) had the high-risk heterozygous genotype, associated with a significant increase in mortality and VAP. Conclusion In 702 trauma patients, 8.3% had a high-risk genetic variation in C2 associated with increased mortality (OR=2.65) and infection (OR=2.00). This variation: 1) Identifies a previously unknown high risk group for infection and mortality; 2) Can be determined on admission; 3) May provide opportunity for early therapeutic intervention; and 4) Requires validation in a distinct cohort of patients. PMID:19430225

The Complement System: A Prey of Trypanosoma cruzi

Directory of Open Access Journals (Sweden)

Kárita C. F. Lidani

2017-04-01

Full Text Available Trypanosoma cruzi is a protozoan parasite known to cause Chagas disease (CD, a neglected sickness that affects around 6–8 million people worldwide. Originally, CD was mainly found in Latin America but more recently, it has been spread to countries in North America, Asia, and Europe due the international migration from endemic areas. Thus, at present CD represents an important concern of global public health. Most of individuals that are infected by T. cruzi may remain in asymptomatic form all lifelong, but up to 40% of them will develop cardiomyopathy, digestive mega syndromes, or both. The interaction between the T. cruzi infective forms and host-related immune factors represents a key point for a better understanding of the physiopathology of CD. In this context, the complement, as one of the first line of host defense against infection was shown to play an important role in recognizing T. cruzi metacyclic trypomastigotes and in controlling parasite invasion. The complement consists of at least 35 or more plasma proteins and cell surface receptors/regulators, which can be activated by three pathways: classical (CP, lectin (LP, and alternative (AP. The CP and LP are mainly initiated by immune complexes or pathogen-associated molecular patterns (PAMPs, respectively, whereas AP is spontaneously activated by hydrolysis of C3. Once activated, several relevant complement functions are generated which include opsonization and phagocytosis of particles or microorganisms and cell lysis. An important step during T. cruzi infection is when intracellular trypomastigotes are release to bloodstream where they may be target by complement. Nevertheless, the parasite uses a sequence of events in order to escape from complement-mediated lysis. In fact, several T. cruzi molecules are known to interfere in the initiation of all three pathways and in the assembly of C3 convertase, a key step in the activation of complement. Moreover, T. cruzi promotes secretion

An Oncogenic Role for Alternative NF-κB Signaling in DLBCL Revealed upon Deregulated BCL6 Expression

Directory of Open Access Journals (Sweden)

Baochun Zhang

2015-05-01

Full Text Available Diffuse large B cell lymphoma (DLBCL is a complex disease comprising diverse subtypes and genetic profiles. Possibly because of the prevalence of genetic alterations activating canonical NF-κB activity, a role for oncogenic lesions that activate the alternative NF-κB pathway in DLBCL has remained elusive. Here, we show that deletion/mutation of TRAF3, a negative regulator of the alternative NF-κB pathway, occurs in ∼15% of DLBCLs and that it often coexists with BCL6 translocation, which prevents terminal B cell differentiation. Accordingly, in a mouse model constitutive activation of the alternative NF-κB pathway cooperates with BCL6 deregulation in DLBCL development. This work demonstrates a key oncogenic role for the alternative NF-κB pathway in DLBCL development.

Regulatory concern about economic deregulation in Finland

International Nuclear Information System (INIS)

Virolainen, R.; Koutaniemi, P.

2002-01-01

The deregulation of the electricity market may cause an increased pressure to reduce the costs of electricity generation. This makes a new challenge to the regulatory body to assess the impact of these changes on the safety of nuclear power plants. Accordingly, it is important to identify the risks to the nuclear power industry resulting from the economic deregulation. This paper is to discuss the current situation in Finland with regard to the economic deregulation of the electricity market and the experiences so far. A common view today is that the number of electricity generating power companies will be reduced in Europe because of tough competition in the electricity market. It is expected that only the biggest companies can stand the consequences of tough competition in electricity prices and the consequential pressure to reduce costs. In order to review the impact of deregulation of the electricity market some relevant points have been discussed in this paper such as change of ownership of power companies due to the economic pressure, the need to cut costs of the companies by reducing the number of their activities and increasing the efficiency in the remaining activities and/or outsourcing of activities. The need to pursue reduction or delay of planned investments in safety upgrades are discussed as well. (author)

Regulatory concern about economic deregulation in Finland

International Nuclear Information System (INIS)

Virolainen, R.; Koutaniemi, P.

2001-01-01

The deregulation of the electricity market may cause an increased pressure to reduce the costs of electricity generation. This makes a new challenge to the regulatory body to assess the impact of these changes on the safety of nuclear power plants. Accordingly, it is important to identify the risks to the nuclear power industry resulting from the economic deregulation. This paper is to discuss the current situation in Finland with regard to the economic deregulation of the electricity market and the experiences so far. A common view today is that the number of electricity generating power companies will be reduced in Europe because of tough competition in the electricity market. It is expected that only the biggest companies can stand the consequences of tough competition in electricity prices and the consequential pressure to reduce costs. In order to review the impact of deregulation of the electricity market some relevant points have been discussed in this paper, such as change of ownership of power companies due to the economic pressure, the need to cut costs of the companies by reducing the number of their activities and increasing the efficiency in the remaining activities and/or outsourcing of activities. The need to pursue reduction or delay of planned investments in safety upgrades are discussed as well. (author)

Bank CEO Pay-Performance Relations and the Effects of Deregulation.

OpenAIRE

Crawford, Anthony J; Ezzell, John R; Miles, James A

1995-01-01

The authors test the deregulation hypothesis that posits that bank CEO compensation became more sensitive to performance as bank management became less regulated. They observe a significant increase in pay-performance sensitivities from their 1976-81 regulation subsample to their 1982-88 deregulation subsample. These increases in pay sensitivities after deregulation are observed for salary and bonus, stock options, and common stock holdings. The authors observe increases in the pay-performanc...

Deregulation of the Nigerian economy: The theoretical milieu

Directory of Open Access Journals (Sweden)

Nureni Opeyemi Akintoye

2014-01-01

Full Text Available The deregulation of Nigerian economy was the main thrust of the Structural Adjustment Programme (SAP introduced in the country in 1986 under the leadership of General Ibrahim Babandiga (1958-1993. Prior to that period the Nigerian economy was almost a command one with wide range of government control. Indeed, the introduction of SAP was said to be a final solution to the economic crisis faced by the Country. Unfortunately, SAP was introduced yet, the economy became more crunched. During the General Abach's regime (1993­1998, SAP was suspended out rightly. When General Abdulsalami Abubakar (1998-1999 took over, he continued pursuing the privatization programme which is a synonym of deregulation of the economy with the promulgation of another privatization decree. The civilian government led by President Obasanjo which took over from 1999 made deregulation the core with vigour. It is basked on this development that this paper intends to unravel the theoretical paradigm under which the deregulation of Nigerian economy could be explained. This includes capitalism, imperialism, colonialism particularly the incorporation of Nigerian into international capitalist system.

What Drives Deregulation? Economics and Politics of the Relaxation of Bank Branching Restrictions

OpenAIRE

Randall S. Kroszner; Philip E. Strahan

1998-01-01

This paper examines the key forces behind deregulation in order to assess the relative importance of alternative theories of regulatory entry and exit. We focus on bank branching deregulation across the states which began a quarter century ago and cumulated in federal deregulation in 1994. The cross-sectional and time-series variation of branching deregulation allows us to develop a hazard model to explain the timing of deregulation across the states using proxies motivated by private-interes...

Alternative complement pathway and factor B activities in rats with altered blood levels of thyroid hormone

Energy Technology Data Exchange (ETDEWEB)

Bitencourt, C.S. [Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Duarte, C.G.; Azzolini, A.E.C.S.; Assis-Pandochi, A.I. [Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil)

2012-03-02

Evaluating the activity of the complement system under conditions of altered thyroid hormone levels might help elucidate the role of complement in triggering autoimmune processes. Here, we investigated alternative pathway (AP) activity in male Wistar rats (180 ± 10 g) after altering their thyroid hormone levels by treatment with triiodothyronine (T3), propylthiouracil (PTU) or thyroidectomy. T3 and thyroxine (T4) levels were determined by chemiluminescence assays. Hemolytic assays were performed to evaluate the lytic activity of the AP. Factor B activity was evaluated using factor B-deficient serum. An anti-human factor B antibody was used to measure factor B levels in serum by radial immunodiffusion. T3 measurements in thyroidectomized animals or animals treated with PTU demonstrated a significant reduction in hormone levels compared to control. The results showed a reduction in AP lytic activity in rats treated with increasing amounts of T3 (1, 10, or 50 µg). Factor B activity was also decreased in the sera of hyperthyroid rats treated with 1 to 50 µg T3. Additionally, treating rats with 25 µg T3 significantly increased factor B levels in their sera (P < 0.01). In contrast, increased factor B concentration and activity (32%) were observed in hypothyroid rats. We conclude that alterations in thyroid hormone levels affect the activity of the AP and factor B, which may in turn affect the roles of AP and factor B in antibody production.

Alternative complement pathway and factor B activities in rats with altered blood levels of thyroid hormone

International Nuclear Information System (INIS)

Bitencourt, C.S.; Duarte, C.G.; Azzolini, A.E.C.S.; Assis-Pandochi, A.I.

2012-01-01

Evaluating the activity of the complement system under conditions of altered thyroid hormone levels might help elucidate the role of complement in triggering autoimmune processes. Here, we investigated alternative pathway (AP) activity in male Wistar rats (180 ± 10 g) after altering their thyroid hormone levels by treatment with triiodothyronine (T3), propylthiouracil (PTU) or thyroidectomy. T3 and thyroxine (T4) levels were determined by chemiluminescence assays. Hemolytic assays were performed to evaluate the lytic activity of the AP. Factor B activity was evaluated using factor B-deficient serum. An anti-human factor B antibody was used to measure factor B levels in serum by radial immunodiffusion. T3 measurements in thyroidectomized animals or animals treated with PTU demonstrated a significant reduction in hormone levels compared to control. The results showed a reduction in AP lytic activity in rats treated with increasing amounts of T3 (1, 10, or 50 µg). Factor B activity was also decreased in the sera of hyperthyroid rats treated with 1 to 50 µg T3. Additionally, treating rats with 25 µg T3 significantly increased factor B levels in their sera (P < 0.01). In contrast, increased factor B concentration and activity (32%) were observed in hypothyroid rats. We conclude that alterations in thyroid hormone levels affect the activity of the AP and factor B, which may in turn affect the roles of AP and factor B in antibody production

European energy markets deregulation observatory. Winter 2002/2003 period

International Nuclear Information System (INIS)

Anon.

2004-01-01

Launched in 2002, the European energy markets deregulation observatory (EEMDO/OELME) aims at actualizing the main energy market indicators and at observing the advance of deregulation within the European countries. While for most of these markets, the deregulation of electricity has preceded the deregulation of gas, the natural gas market is at the evidence a key-market in Europe. For this reason, the 4. edition of the observatory (October 2003) takes into consideration for the first time the specific elements of gas markets, in addition to those of electricity markets. This article presents some excerpts of this last edition, published by Cap Gemini Ernst and Young, and synthesizes the present day situation of gas supplies and the conditions of network access by third parties. The informations reported in the EEMDO come from organizations like UCTE, Nordel, Eurelectric or from energy stock exchanges. (J.S.)

Crosstalk between Complement and Toll-like Receptor Activation in Relation to Donor Brain Death and Renal Ischemia-Reperfusion Injury

NARCIS (Netherlands)

Damman, Jeffrey; Daha, Mohamed R.; van Son, Willem J.; Leuvenink, Henri G.; Ploeg, Rutger J.; Seelen, Marc A.

Two central pathways of innate immunity, complement and Toll-like receptors (TLRs), play an important role in the pathogenesis of renal injury inherent to kidney transplantation. Recent findings indicate close crosstalk between complement and TLR signaling pathways. It is suggested that mitogen

The long-run price sensitivity dynamics of industrial and residential electricity demand: The impact of deregulating electricity prices

International Nuclear Information System (INIS)

Adom, Philip Kofi

2017-01-01

This study examines the demand-side of Ghana's electricity sector. We test two important related hypotheses: (1) deregulation of electricity price does not promote energy conservation, and (2) demand-price relationship is not an inverted U-shaped. The Stock and Watson dynamic OLS is used to address the so-called second-order bias. The result showed that, deregulation of electricity price in Ghana has induced behaviours that are more consistent with energy conservation improvements. The demand-price relationship is an inverted U, which suggests that there is a price range that end-users can tolerate further price rise and still increase their consumption of electricity. However, the degree of price tolerability is higher for residential consumers than industrial consumers. The simulation results showed that, further economic growth is likely to compromise energy conservation but more in the industrial sector than the residential sector. On the other hand, future crude oil price is likely to deteriorate energy conservation in the initial years after 2016, but this trend is likely to reverse after the year 2020. Pricing mechanisms are potent to induce energy conservation but inadequate. The results suggest that they should be complemented with other stringent policies such as a mandatory energy reduction policy, investment in renewables, and personalization of energy efficiency programs. - Highlights: • Studies the demand-side of the electricity sector • Deregulating electricity price promotes energy conservation • Demand-price relationship is an inverted U-shaped • Pricing policies should be combined with other energy mandatory reduction policies

Efficiency and deregulation of the electricity market in Singapore

International Nuclear Information System (INIS)

Youngho Chang; Tuan Hin Tay

2006-01-01

This study examines production efficiency of electricity generation in the New Electricity Market of Singapore (NEMS), where deregulation is currently proceeding. Singapore is reliant on foreign direct investments and exports so competition from countries with lower costs such as China and India is exerting pressure on the government to reduce the costs of doing business here. Electricity cost is one of these. Deregulation is believed to be able to bring about lower electricity costs due to the various efficiency gains possible. This study concerns itself mainly with production efficiency and attempts to calculate possible production efficiency gains by using linear programming model. Production-efficiency gains are quantified by the base case scenario of continued regulation versus four counterfactual deregulation scenarios. The results indicate that cost gains could be about eight per cent of current production cost, and this is possibly a lower-bound estimate. However, whether the purported efficiency gains are realized is to be seen as the deregulation proceeds. (author)

Efficiency and deregulation of the electricity market in Singapore

International Nuclear Information System (INIS)

Chang, Youngho; Hin Tay, Tuan

2006-01-01

This study examines production efficiency of electricity generation in the New Electricity Market of Singapore (NEMS), where deregulation is currently proceeding. Singapore is reliant on foreign direct investments and exports so competition from countries with lower costs such as China and India is exerting pressure on the government to reduce the costs of doing business here. Electricity cost is one of these. Deregulation is believed to be able to bring about lower electricity costs due to the various efficiency gains possible. This study concerns itself mainly with production efficiency and attempts to calculate possible production efficiency gains by using linear programming model. Production-efficiency gains are quantified by the base case scenario of continued regulation versus four counterfactual deregulation scenarios. The results indicate that cost gains could be about eight per cent of current production cost, and this is possibly a lower-bound estimate. However, whether the purported efficiency gains are realized is to be seen as the deregulation proceeds

Retail experience in the de-regulated market

International Nuclear Information System (INIS)

Cummings, R.

2003-01-01

This paper describes the experience gained to date in the de-regulated electricity market through an examination of the commercial market. In 2001, chaos provided opportunity, while in 2002 the emphasis was on operations. In 2003, the landscape reflected hyper-competition, selling second services, and a changing landscape. A discussion followed on the residential market with a look at market structure, economics, and uncertainty concerning the future. The following components were identified as working well: wholesale market, commercial market, market model/data, and innovation in offerings and green supply. Areas requiring further improvement were also identified. It was suggested that the residential de-regulated roadmap should be clarified and retail friendly transactions should be imposed. Other improvements involve education and operations/system capabilities. The author concluded that the deregulated electricity market is still an immature market, where progress is being made in the commercial market. The residential market is in a critical period, with a market model still evolving. figs

Association between lectin complement pathway initiators, C-reactive protein and left ventricular remodeling in myocardial infarction-a magnetic resonance study

DEFF Research Database (Denmark)

Schoos, Mikkel Malby; Munthe-Fog, Lea; Skjoedt, Mikkel-Ole

2013-01-01

Lectin complement pathway (LP) activation is an important mechanism in myocardial ischemia reperfusion injury (IRI). LP is activated via the recognition molecules mannose-binding lectin (MBL), ficolins-2 and-3 and is regulated by MBL/Ficolin-associated Protein-1 (MAP-1). Also, C-reactive protein...... (CRP) and ficolin-2 interact in vitro, but the role of the ficolins in IRI is unknown.Methods and results In 55 patients with ST segment elevation myocardial infarction, we investigated the association of LP components and CRP in plasma samples with left ventricular (LV) end systolic and diastolic......-activation in IRI and LV remodeling....

Deregulation of an imprinted gene network in prostate cancer.

Science.gov (United States)

Ribarska, Teodora; Goering, Wolfgang; Droop, Johanna; Bastian, Klaus-Marius; Ingenwerth, Marc; Schulz, Wolfgang A

2014-05-01

Multiple epigenetic alterations contribute to prostate cancer progression by deregulating gene expression. Epigenetic mechanisms, especially differential DNA methylation at imprinting control regions (termed DMRs), normally ensure the exclusive expression of imprinted genes from one specific parental allele. We therefore wondered to which extent imprinted genes become deregulated in prostate cancer and, if so, whether deregulation is due to altered DNA methylation at DMRs. Therefore, we selected presumptive deregulated imprinted genes from a previously conducted in silico analysis and from the literature and analyzed their expression in prostate cancer tissues by qRT-PCR. We found significantly diminished expression of PLAGL1/ZAC1, MEG3, NDN, CDKN1C, IGF2, and H19, while LIT1 was significantly overexpressed. The PPP1R9A gene, which is imprinted in selected tissues only, was strongly overexpressed, but was expressed biallelically in benign and cancerous prostatic tissues. Expression of many of these genes was strongly correlated, suggesting co-regulation, as in an imprinted gene network (IGN) reported in mice. Deregulation of the network genes also correlated with EZH2 and HOXC6 overexpression. Pyrosequencing analysis of all relevant DMRs revealed generally stable DNA methylation between benign and cancerous prostatic tissues, but frequent hypo- and hyper-methylation was observed at the H19 DMR in both benign and cancerous tissues. Re-expression of the ZAC1 transcription factor induced H19, CDKN1C and IGF2, supporting its function as a nodal regulator of the IGN. Our results indicate that a group of imprinted genes are coordinately deregulated in prostate cancers, independently of DNA methylation changes.

Gas and electricity 2000: energy deregulation

International Nuclear Information System (INIS)

Hulot, J.C.; Charbit, N.; Tuot, Th.

2000-11-01

This document brings together 17 testimonies of experts about the deregulation of the gas and electricity markets. Content: 1 - the new rules controlling the market: schedule and regulatory evolutions, the new legal framework, the new regulation, the missions and competences of the Commission of Electricity Regulation; 2 - the new commercial practices: the question of electricity transport and of the network independence, the development of trading, the stock exchanges and the forecasting of Paris market, the correlations with the environment (eco-taxes and climate change); 3 - the proposals of new actors: the contribution of a deregulated market like Spain, the comparison with a fully open market like Germany, an internal out-sourcing example to create an energy entity as a whole, the role of a bank in the risk management and the derived markets, the contribution of new technologies from service suppliers; 4 - the consumers attitude with respect to new offers: the historical gas and electricity utilities at the service of French and European clients, the new opportunities offered by the deregulation, the contribution of an independent supplier to consumers, the expectations of big companies and eligible consumers. (J.S.)

Natural gas and deregulation in the European Market

International Nuclear Information System (INIS)

Anon.

2000-01-01

The gas market is progressively moving towards new organizations under the effect of deregulation initiated in the United States, the United Kingdom and transposed to other countries, particularly in Europe, at least for the member countries of the European Union. Within the framework provided by this overall trend, Cedigaz proposes a study titled 'Natural Gas and Deregulation' in order to describe the main developments affecting these markets on account of deregulation. This report is structured on the basis of three main topics (market organization, marketing modes, pricing) which appears to be the most cogent in terms of deregulation. This grouping by major topics accordingly offers a relatively synthetic view of the main trends which could be observed in the European market, for example. The analysis is largely based on the example of the American market and, to a lesser extent, on the British situation. Incidentally, it has adapted the terms 'regulated market' to define conventional markets and 'deregulated market' to define markets which have incorporated the principle of Third Party Access (TPA). This is obviously a mere convention, since in both cases, the gas market, a network market, is regulated either by the State or by an independent agency. Also noteworthy is the diversity of the regulation methods for the network markets. While an underlying principle prevails throughout, particularly the introduction of TPA, political and energy considerations alike are liable to condition strongly the final structure of a given market. The apparently comparable British and American experience thus display substantial differences. In other words, one should not imagine a sudden transposition of either case to the European market. The different States preserve considerable leeway to guide market developments in one direction or another. On the whole, deregulation is not a frozen process, but has to adapt permanently to developments in a market stage-managed by

A law enforcement perspective of electricity deregulation

International Nuclear Information System (INIS)

Horowitz, Ira

2006-01-01

In April 2004, the California Attorney General's (AG) office issued a white paper that provided a 'law enforcement perspective of the California energy crisis.' To complete this special issue's coverage, I summarize three aspects of that paper: notably, the deficiencies in market oversight and enforcement that left the deregulated market prone to potential abuse, the principal modus operandi that some market agents used to exploit those deficiencies without fear of retribution, and the AG's 'recommendations for improving enforcement and protecting consumers in deregulated energy markets.'. (author)

Complements and the Wound Healing Cascade: An Updated Review

Directory of Open Access Journals (Sweden)

Hani Sinno

2013-01-01

Full Text Available Wound healing is a complex pathway of regulated reactions and cellular infiltrates. The mechanisms at play have been thoroughly studied but there is much still to learn. The health care system in the USA alone spends on average 9 billion dollars annually on treating of wounds. To help reduce patient morbidity and mortality related to abnormal or prolonged skin healing, an updated review and understanding of wound healing is essential. Recent works have helped shape the multistep process in wound healing and introduced various growth factors that can augment this process. The complement cascade has been shown to have a role in inflammation and has only recently been shown to augment wound healing. In this review, we have outlined the biology of wound healing and discussed the use of growth factors and the role of complements in this intricate pathway.

Complement Involvement in Periodontitis: Molecular Mechanisms and Rational Therapeutic Approaches.

Science.gov (United States)

Hajishengallis, George; Maekawa, Tomoki; Abe, Toshiharu; Hajishengallis, Evlambia; Lambris, John D

2015-01-01

The complement system is a network of interacting fluid-phase and cell surface-associated molecules that trigger, amplify, and regulate immune and inflammatory signaling pathways. Dysregulation of this finely balanced network can destabilize host-microbe homeostasis and cause inflammatory tissue damage. Evidence from clinical and animal model-based studies suggests that complement is implicated in the pathogenesis of periodontitis, a polymicrobial community-induced chronic inflammatory disease that destroys the tooth-supporting tissues. This review discusses molecular mechanisms of complement involvement in the dysbiotic transformation of the periodontal microbiome and the resulting destructive inflammation, culminating in loss of periodontal bone support. These mechanistic studies have additionally identified potential therapeutic targets. In this regard, interventional studies in preclinical models have provided proof-of-concept for using complement inhibitors for the treatment of human periodontitis.

Combined roles of human IgG subclass, alternative complement pathway activation, and epitope density in the bactericidal activity of antibodies to meningococcal factor h binding protein.

Science.gov (United States)

Giuntini, Serena; Reason, Donald C; Granoff, Dan M

2012-01-01

Meningococcal vaccines containing factor H binding protein (fHbp) are in clinical development. fHbp binds human fH, which enables the meningococcus to resist complement-mediated bacteriolysis. Previously, we found that chimeric human IgG1 mouse anti-fHbp monoclonal antibodies (MAbs) had human complement-mediated bactericidal activity only if the MAb inhibited fH binding. Since IgG subclasses differ in their ability to activate complement, we investigated the role of human IgG subclasses on antibody functional activity. We constructed chimeric MAbs in which three different murine fHbp-specific binding domains were each paired with human IgG1, IgG2, or IgG3. Against a wild-type group B isolate, all three IgG3 MAbs, irrespective of their ability to inhibit fH binding, had bactericidal activity that was >5-fold higher than the respective IgG1 MAbs, while the IgG2 MAbs had the least activity. Against a mutant with increased fHbp expression, the anti-fHbp MAbs elicited greater C4b deposition (classical pathway) and greater bactericidal activity than against the wild-type strain, and the IgG1 MAbs had similar or greater activity than the respective IgG3 MAbs. The bactericidal activity against both wild-type and mutant strains also was dependent, in part, on activation of the alternative complement pathway. Thus, at lower epitope density in the wild-type strain, the IgG3 anti-fHbp MAbs had the greatest bactericidal activity. At a higher epitope density in the mutant, the IgG1 MAbs had similar or greater bactericidal activity than the IgG3 MAbs, and the activity was less dependent on the inhibition of fH binding than at a lower epitope density.

Different host complement systems and their interactions with saliva from Lutzomyia longipalpis (Diptera, Psychodidae) and Leishmania infantum promastigotes.

Science.gov (United States)

Mendes-Sousa, Antonio Ferreira; Nascimento, Alexandre Alves Sousa; Queiroz, Daniel Costa; Vale, Vladimir Fazito; Fujiwara, Ricardo Toshio; Araújo, Ricardo Nascimento; Pereira, Marcos Horácio; Gontijo, Nelder Figueiredo

2013-01-01

Lutzomyia longipalpis is the vector of Leishmania infantum in the New World, and its saliva inhibits classical and alternative human complement system pathways. This inhibition is important in protecting the insect´s midgut from damage by the complement. L. longipalpis is a promiscuous blood feeder and must be protected against its host's complement. The objective of this study was to investigate the action of salivary complement inhibitors on the sera of different host species, such as dogs, guinea pigs, rats and chickens, at a pH of 7.4 (normal blood pH) and 8.15 (the midgut pH immediately after a blood meal). We also investigated the role of the chicken complement system in Leishmania clearance in the presence and absence of vector saliva. The saliva was capable of inhibiting classical pathways in dogs, guinea pigs and rats at both pHs. The alternative pathway was not inhibited except in dogs at a pH of 8.15. The chicken classical pathway was inhibited only by high concentrations of saliva and it was better inhibited by the midgut contents of sand flies. Neither the saliva nor the midgut contents had any effect on the avian alternative pathway. Fowl sera killed L. infantum promastigotes, even at a low concentration (2%), and the addition of L. longipalpis saliva did not protect the parasites. The high body temperature of chickens (40°C) had no effect on Leishmania viability during our assays. Salivary inhibitors act in a species-specific manner. It is important to determine their effects in the natural hosts of Leishmania infantum because they act on canid and rodent complements but not on chickens (which do not harbour the parasite). Moreover, we concluded that the avian complement system is the probable mechanism through which chickens eliminate Leishmania and that their high body temperature does not influence this parasite.

Reincarnation of ancient links between coagulation and complement.

Science.gov (United States)

Conway, E M

2015-06-01

Throughout evolution, organisms have developed means to contain wounds by simultaneously limiting bleeding and eliminating pathogens and damaged host cells via the recruitment of innate defense mechanisms. Disease emerges when there is unchecked activation of innate immune and/or coagulation responses. A key component of innate immunity is the complement system. Concurrent excess activation of coagulation and complement - two major blood-borne proteolytic pathways - is evident in numerous diseases, including atherosclerosis, diabetes, venous thromboembolic disease, thrombotic microangiopathies, arthritis, cancer, and infectious diseases. Delineating the cross-talk between these two cascades will uncover novel therapeutic insights. © 2015 International Society on Thrombosis and Haemostasis.

Electricity utility deregulation in Great Britain: economic and industrial consequences

International Nuclear Information System (INIS)

Anon.

1993-01-01

In this paper we analyze in the first part how was made the deregulation of the public electric utilities in Great Britain and in the second the logic and the contradictions of this deregulation in an industrial point of view

Deregulation and the Alberta experience : the implications for Ontario

Energy Technology Data Exchange (ETDEWEB)

Spearman, C. [Industrial Association of Southern Alberta, Lethbridge, AB (Canada)

2002-07-01

The government of Alberta deregulated its electric power industry to introduce industry structure and regulatory reforms that would promote competitive electricity prices. The objective was to ensure fairness for customers and generating facilities. A graph depicting power pool prices shows the reality of soaring prices at the onset of deregulation in Alberta. Today, there remains uncertainty in the development of retail choice, additional rate riders, new generation, transmission expansion, other jurisdictions and future prices. Consumers are still poorly equipped to make decisions and farmers have no means of protection from fluctuating electricity prices. They see deregulation as a complete failure because costs are up and benefits are nowhere to be seen. Ontario can learn from the Alberta experience by adopting the recommendations to set financial penalties for incompetence, financial compensation to customers for errors, and to be fully ready with systems tested ahead of deregulation. Anticipated customer benefits should be clearly identified in advance. The future electric power industry in Ontario needs vision, stability, a cohesive plan, and leadership devoid of complacency. 1 fig.

Deregulation and the Alberta experience : the implications for Ontario

International Nuclear Information System (INIS)

Spearman, C.

2002-01-01

The government of Alberta deregulated its electric power industry to introduce industry structure and regulatory reforms that would promote competitive electricity prices. The objective was to ensure fairness for customers and generating facilities. A graph depicting power pool prices shows the reality of soaring prices at the onset of deregulation in Alberta. Today, there remains uncertainty in the development of retail choice, additional rate riders, new generation, transmission expansion, other jurisdictions and future prices. Consumers are still poorly equipped to make decisions and farmers have no means of protection from fluctuating electricity prices. They see deregulation as a complete failure because costs are up and benefits are nowhere to be seen. Ontario can learn from the Alberta experience by adopting the recommendations to set financial penalties for incompetence, financial compensation to customers for errors, and to be fully ready with systems tested ahead of deregulation. Anticipated customer benefits should be clearly identified in advance. The future electric power industry in Ontario needs vision, stability, a cohesive plan, and leadership devoid of complacency. 1 fig

Complement-dependent transport of antigen into B cell follicles

DEFF Research Database (Denmark)

Gonzalez, Santiago F.; Lukacs-Kornek, Veronika; Kuligowski, Michael P.

2010-01-01

an additional novel pathway in which complement C3 and its receptors enhance humoral immunity through delivery of Ag to the B cell compartment. In this review, we discuss this pathway and highlight several novel exceptions recently found with a model influenza vaccine, such as mannose-binding lectin...... opsonization of influenza and uptake by macrophages, and the capture of virus by dendritic cells residing in the medullary compartment of peripheral lymph nodes....

Micrurus snake venoms activate human complement system and generate anaphylatoxins

Directory of Open Access Journals (Sweden)

Tanaka Gabriela D

2012-01-01

Full Text Available Abstract Background The genus Micrurus, coral snakes (Serpentes, Elapidae, comprises more than 120 species and subspecies distributed from the south United States to the south of South America. Micrurus snake bites can cause death by muscle paralysis and further respiratory arrest within a few hours after envenomation. Clinical observations show mainly neurotoxic symptoms, although other biological activities have also been experimentally observed, including cardiotoxicity, hemolysis, edema and myotoxicity. Results In the present study we have investigated the action of venoms from seven species of snakes from the genus Micrurus on the complement system in in vitro studies. Several of the Micrurus species could consume the classical and/or the lectin pathways, but not the alternative pathway, and C3a, C4a and C5a were generated in sera treated with the venoms as result of this complement activation. Micrurus venoms were also able to directly cleave the α chain of the component C3, but not of the C4, which was inhibited by 1,10 Phenanthroline, suggesting the presence of a C3α chain specific metalloprotease in Micrurus spp venoms. Furthermore, complement activation was in part associated with the cleavage of C1-Inhibitor by protease(s present in the venoms, which disrupts complement activation control. Conclusion Micrurus venoms can activate the complement system, generating a significant amount of anaphylatoxins, which may assist due to their vasodilatory effects, to enhance the spreading of other venom components during the envenomation process.

Crosstalk between complement and Toll-like receptor activation in relation to donor brain death and renal ischemia-reperfusion injury.

Science.gov (United States)

Damman, Jeffrey; Daha, Mohamed R; van Son, Willem J; Leuvenink, Henri G; Ploeg, Rutger J; Seelen, Marc A

2011-04-01

Two central pathways of innate immunity, complement and Toll-like receptors (TLRs), play an important role in the pathogenesis of renal injury inherent to kidney transplantation. Recent findings indicate close crosstalk between complement and TLR signaling pathways. It is suggested that mitogen activated protein kinases (MAPKs) might be the key molecules linking both the complement and TLR pathways together. Complement and TLRs are important mediators of renal ischemia-reperfusion injury (IRI). Besides IRI, complement C3 can also be upregulated and activated in the kidney before transplantation as a direct result of brain death (BD) in the donor. This local upregulation and activation of complement in the donor kidney has been proven to be detrimental for renal allograft outcome. Also TLR4 and several of its major ligands are upregulated by donor BD compared to living donors. Important and in line with the observations above, kidney transplant recipients have a benefit when receiving a kidney from a TLR4 Asp299Gly/Thr399Ile genotypic donor. The role of complement and TLRs and crosstalk between these two innate immune systems in relation to renal injury during donor BD and ischemia-reperfusion are focus of this review. Future strategies to target complement and TLR activation in kidney transplantation are considered. ©2011 The Authors Journal compilation©2011 The American Society of Transplantation and the American Society of Transplant Surgeons.

Serum complement changes during double-blind food challenges in children with a history of food sensitivity.

Science.gov (United States)

Martin, M E; Guthrie, L A; Bock, S A

1984-04-01

Serum levels of C3, C4, factor B, properdin, total hemolytic complement and alternative-pathway hemolytic activity were measured before and after double-blind food challenge in 23 children with impressive histories of adverse reactions to foods. The 23 subjects had 11 positive food challenges and 12 negative food challenges. Nine patients with reagin-mediated positive food challenges showed increases in all six complement assays after double-blind food challenge, while the group with negative food challenges showed decreases in five of the six assays. The difference between the two groups for complement changes after double-blind food challenge was significant only for the alternative-pathway assay. Individual subject analysis revealed markedly heterogeneous changes in direction and magnitude within both groups for all complement assays. Therefore, it is concluded that measurement of serum complement levels is not a useful test for the clinical evaluation of a patient with suspected food sensitivity.

Deregulation of the European Banking Industry (1980-1991)

OpenAIRE

Gual, Jordi; Neven, Damien J

1992-01-01

In this paper the experience of deregulation in the banking sector of seven EC countries (Belgium, France, Germany, Italy, the Netherlands, Spain and the UK) is analysed. Lessons are drawn for assessment of how the EC directives affecting this sector could further affect the industry. Our findings broadly confirm intuition: there is some evidence that firms in protected markets earn large rents, which are partly dissipated in excessive costs and captured by workers. Conduct deregulation seems...

Why Shops Close Again : An Evolutionary Perspective on the Deregulation of Shopping Hours

NARCIS (Netherlands)

Kosfeld, M.

1999-01-01

This paper introduces a new perspective on the deregulation of shopping hours based on ideas from evolutionary game theory. We study a retail economy where shopping hours have been deregulated recently. It is argued that first, the deregulation leads to a coordination problem between store owners

Targeting Apoptosis Signaling Pathways for Anticancer Therapy

Energy Technology Data Exchange (ETDEWEB)

Fulda, Simone, E-mail: simone.fulda@kgu.de [Institute for Experimental Cancer Research in Pediatrics, Goethe-University, Frankfurt (Germany)

2011-08-29

Treatment approaches for cancer, for example chemotherapy, radiotherapy, or immunotherapy, primarily act by inducing cell death in cancer cells. Consequently, the inability to trigger cell death pathways or alternatively, evasion of cancer cells to the induction of cell death pathways can result in resistance of cancers to current treatment protocols. Therefore, in order to overcome treatment resistance a better understanding of the underlying mechanisms that regulate cell death and survival pathways in cancers and in response to cancer therapy is necessary to develop molecular-targeted therapies. This strategy should lead to more effective and individualized treatment strategies that selectively target deregulated signaling pathways in a tumor type- and patient-specific manner.

Targeting Apoptosis Signaling Pathways for Anticancer Therapy

International Nuclear Information System (INIS)

Fulda, Simone

2011-01-01

Treatment approaches for cancer, for example chemotherapy, radiotherapy, or immunotherapy, primarily act by inducing cell death in cancer cells. Consequently, the inability to trigger cell death pathways or alternatively, evasion of cancer cells to the induction of cell death pathways can result in resistance of cancers to current treatment protocols. Therefore, in order to overcome treatment resistance a better understanding of the underlying mechanisms that regulate cell death and survival pathways in cancers and in response to cancer therapy is necessary to develop molecular-targeted therapies. This strategy should lead to more effective and individualized treatment strategies that selectively target deregulated signaling pathways in a tumor type- and patient-specific manner.

Novel roles of complement in renal diseases and their therapeutic consequences.

Science.gov (United States)

Wada, Takehiko; Nangaku, Masaomi

2013-09-01

The complement system functions as a part of the innate immune system. Inappropriate activation of the complement pathways has a deleterious effect on kidneys. Recent advances in complement research have provided new insights into the pathogenesis of glomerular and tubulointerstitial injury associated with complement activation. A new disease entity termed 'C3 glomerulopathy' has recently been proposed and is characterized by isolated C3 deposition in glomeruli without positive staining for immunoglobulins. Genetic and functional studies have demonstrated that several different mutations and disease variants, as well as the generation of autoantibodies, are potentially associated with its pathogenesis. The data from comprehensive analyses suggest that complement dysregulation can also be associated with hemolytic uremic syndrome and more common glomerular diseases, such as IgA nephropathy and diabetic kidney disease. In addition, animal studies utilizing genetically modified mice have begun to elucidate the molecular pathomechanisms associated with the complement system. From a diagnostic point of view, a noninvasive, MRI-based method for detecting C3 has recently been developed to serve as a novel tool for diagnosing complement-mediated kidney diseases. While novel therapeutic tools related to complement regulation are emerging, studies evaluating the precise roles of the complement system in kidney diseases will still be useful for developing new therapeutic approaches.

Studies of the binding of ficolin-2 and ficolin-3 from the complement lectin pathway to Leptospira biflexa, Pasteurella pneumotropica and Diarrheagenic Escherichia coli

DEFF Research Database (Denmark)

Sahagún-Ruiz, Alfredo; Breda, Leandro Carvalho Dantas; Valencia, Mónica Marcela Castiblanco

2015-01-01

Ficolins recognize pathogen associated molecular patterns and activate the lectin pathway of complement system. However, our knowledge regarding pathogen recognition of human ficolins is still limited. We therefore set out to explore and investigate the possible interactions of the two main serum...

Human factor H-related protein 2 (CFHR2 regulates complement activation.

Directory of Open Access Journals (Sweden)

Hannes U Eberhardt

Full Text Available Mutations and deletions within the human CFHR gene cluster on chromosome 1 are associated with diseases, such as dense deposit disease, CFHR nephropathy or age-related macular degeneration. Resulting mutant CFHR proteins can affect complement regulation. Here we identify human CFHR2 as a novel alternative pathway complement regulator that inhibits the C3 alternative pathway convertase and terminal pathway assembly. CFHR2 is composed of four short consensus repeat domains (SCRs. Two CFHR2 molecules form a dimer through their N-terminal SCRs, and each of the two C-terminal ends can bind C3b. C3b bound CFHR2 still allows C3 convertase formation but the CFHR2 bound convertases do not cleave the substrate C3. Interestingly CFHR2 hardly competes off factor H from C3b. Thus CFHR2 likely acts in concert with factor H, as CFHR2 inhibits convertases while simultaneously allowing factor H assisted degradation by factor I.

Gene Expression Profiling Reveals a Massive, Aneuploidy-Dependent Transcriptional Deregulation and Distinct Differences between Lymph Node–Negative and Lymph Node–Positive Colon Carcinomas

Science.gov (United States)

Grade, Marian; Hörmann, Patrick; Becker, Sandra; Hummon, Amanda B.; Wangsa, Danny; Varma, Sudhir; Simon, Richard; Liersch, Torsten; Becker, Heinz; Difilippantonio, Michael J.; Ghadimi, B. Michael; Ried, Thomas

2016-01-01

To characterize patterns of global transcriptional deregulation in primary colon carcinomas, we did gene expression profiling of 73 tumors [Unio Internationale Contra Cancrum stage II (n = 33) and stage III (n = 40)] using oligonucleotide microarrays. For 30 of the tumors, expression profiles were compared with those from matched normal mucosa samples. We identified a set of 1,950 genes with highly significant deregulation between tumors and mucosa samples (P 5-fold average expression difference between normal colon mucosa and carcinomas, including up-regulation of MYC and of HMGA1, a putative oncogene. Furthermore, we identified 68 genes that were significantly differentially expressed between lymph node–negative and lymph node–positive tumors (P deregulated genes were validated using quantitative real-time reverse transcription-PCR in >40 tumor and normal mucosa samples with good concordance between the techniques. Finally, we established a relationship between specific genomic imbalances, which were mapped for 32 of the analyzed colon tumors by comparative genomic hybridization, and alterations of global transcriptional activity. Previously, we had conducted a similar analysis of primary rectal carcinomas. The systematic comparison of colon and rectal carcinomas revealed a significant overlap of genomic imbalances and transcriptional deregulation, including activation of the Wnt/β-catenin signaling cascade, suggesting similar pathogenic pathways. PMID:17210682

The complement system: a gateway to gene-environment interactions in schizophrenia pathogenesis.

Science.gov (United States)

Nimgaonkar, V L; Prasad, K M; Chowdari, K V; Severance, E G; Yolken, R H

2017-11-01

The pathogenesis of schizophrenia is considered to be multi-factorial, with likely gene-environment interactions (GEI). Genetic and environmental risk factors are being identified with increasing frequency, yet their very number vastly increases the scope of possible GEI, making it difficult to identify them with certainty. Accumulating evidence suggests a dysregulated complement pathway among the pathogenic processes of schizophrenia. The complement pathway mediates innate and acquired immunity, and its activation drives the removal of damaged cells, autoantigens and environmentally derived antigens. Abnormalities in complement functions occur in many infectious and autoimmune disorders that have been linked to schizophrenia. Many older reports indicate altered serum complement activity in schizophrenia, though the data are inconclusive. Compellingly, recent genome-wide association studies suggest repeat polymorphisms incorporating the complement 4A (C4A) and 4B (C4B) genes as risk factors for schizophrenia. The C4A/C4B genetic associations have re-ignited interest not only in inflammation-related models for schizophrenia pathogenesis, but also in neurodevelopmental theories, because rodent models indicate a role for complement proteins in synaptic pruning and neurodevelopment. Thus, the complement system could be used as one of the 'staging posts' for a variety of focused studies of schizophrenia pathogenesis. They include GEI studies of the C4A/C4B repeat polymorphisms in relation to inflammation-related or infectious processes, animal model studies and tests of hypotheses linked to autoimmune diseases that can co-segregate with schizophrenia. If they can be replicated, such studies would vastly improve our understanding of pathogenic processes in schizophrenia through GEI analyses and open new avenues for therapy.

M. leprae components induce nerve damage by complement activation: identification of lipoarabinomannan as the dominant complement activator.

Science.gov (United States)

Bahia El Idrissi, Nawal; Das, Pranab K; Fluiter, Kees; Rosa, Patricia S; Vreijling, Jeroen; Troost, Dirk; Morgan, B Paul; Baas, Frank; Ramaglia, Valeria

2015-05-01

Peripheral nerve damage is the hallmark of leprosy pathology but its etiology is unclear. We previously identified the membrane attack complex (MAC) of the complement system as a key determinant of post-traumatic nerve damage and demonstrated that its inhibition is neuroprotective. Here, we determined the contribution of the MAC to nerve damage caused by Mycobacterium leprae and its components in mouse. Furthermore, we studied the association between MAC and the key M. leprae component lipoarabinomannan (LAM) in nerve biopsies of leprosy patients. Intraneural injections of M. leprae sonicate induced MAC deposition and pathological changes in the mouse nerve, whereas MAC inhibition preserved myelin and axons. Complement activation occurred mainly via the lectin pathway and the principal activator was LAM. In leprosy nerves, the extent of LAM and MAC immunoreactivity was robust and significantly higher in multibacillary compared to paucibacillary donors (p = 0.01 and p = 0.001, respectively), with a highly significant association between LAM and MAC in the diseased samples (r = 0.9601, p = 0.0001). Further, MAC co-localized with LAM on axons, pointing to a role for this M. leprae antigen in complement activation and nerve damage in leprosy. Our findings demonstrate that MAC contributes to nerve damage in a model of M. leprae-induced nerve injury and its inhibition is neuroprotective. In addition, our data identified LAM as the key pathogen associated molecule that activates complement and causes nerve damage. Taken together our data imply an important role of complement in nerve damage in leprosy and may inform the development of novel therapeutics for patients.

The paralogous salivary anti-complement proteins IRAC I and IRAC II encoded by Ixodes ricinus ticks have broad and complementary inhibitory activities against the complement of different host species.

Science.gov (United States)

Schroeder, Hélène; Daix, Virginie; Gillet, Laurent; Renauld, Jean-Christophe; Vanderplasschen, Alain

2007-02-01

Several observations suggest that inhibition of the host complement alternative pathway by Ixodes tick saliva is crucial to achieve blood feeding. We recently described two paralogous anti-complement proteins called Ixodes ricinus anti-complement (IRAC) proteins I and II co-expressed in I. ricinus salivary glands. Phylogenetic analyses suggested that these sequences were diversifying by a process of positive Darwinian selection, possibly leading to molecules with different biological properties. In the present study, we tested the hypothesis that each paralogue may have different inhibitory activities against the complement of different natural host species, thereby contributing to broaden the host range of I. ricinus ticks. IRAC I and IRAC II were tested against the complement of eight I. ricinus natural host species (six mammals and two birds). The results demonstrate that IRAC I and IRAC II have broad and complementary inhibition activities against the complement of different host species. This report is the first description of paralogous anti-complement molecules encoded by a pathogen with broad and complementary inhibitory activities against the complement of different host species.

A law enforcement perspective of electricity deregulation

Energy Technology Data Exchange (ETDEWEB)

Horowitz, Ira [Warrington College of Business, University of Florida, Gainesville, FL 32611-7169 (United States)

2006-05-15

In April 2004, the California Attorney General's (AG) office issued a white paper that provided a 'law enforcement perspective of the California energy crisis.' To complete this special issue's coverage, I summarize three aspects of that paper: notably, the deficiencies in market oversight and enforcement that left the deregulated market prone to potential abuse, the principal modus operandi that some market agents used to exploit those deficiencies without fear of retribution, and the AG's 'recommendations for improving enforcement and protecting consumers in deregulated energy markets.'. (author)

Functional analysis of Ficolin-3 mediated complement activation

DEFF Research Database (Denmark)

Hein, Estrid; Honoré, Christian Le Fèvre; Skjoedt, Mikkel-Ole

2010-01-01

assessed by C4, C3 and terminal complement complex (TCC) deposition. Serum Ficolin-3 bound to acBSA in a calcium dependent manner, while only minimal binding of Ficolin-2 and no binding of Ficolin-1 were observed. No binding to normal BSA was seen for any of the Ficolins. Serum C4, C3 and TCC deposition...... was applied to the samples that inhibited interference from the classical pathway due to the presence of anti-BSA antibodies in some sera. We describe a novel functional method for measuring complement activation mediated by Ficolin-3 in human serum up to the formation of TCC. The assay provides...

Different host complement systems and their interactions with saliva from Lutzomyia longipalpis (Diptera, Psychodidae and Leishmania infantum promastigotes.

Directory of Open Access Journals (Sweden)

Antonio Ferreira Mendes-Sousa

Full Text Available BACKGROUND: Lutzomyia longipalpis is the vector of Leishmania infantum in the New World, and its saliva inhibits classical and alternative human complement system pathways. This inhibition is important in protecting the insect´s midgut from damage by the complement. L. longipalpis is a promiscuous blood feeder and must be protected against its host's complement. The objective of this study was to investigate the action of salivary complement inhibitors on the sera of different host species, such as dogs, guinea pigs, rats and chickens, at a pH of 7.4 (normal blood pH and 8.15 (the midgut pH immediately after a blood meal. We also investigated the role of the chicken complement system in Leishmania clearance in the presence and absence of vector saliva. RESULTS: The saliva was capable of inhibiting classical pathways in dogs, guinea pigs and rats at both pHs. The alternative pathway was not inhibited except in dogs at a pH of 8.15. The chicken classical pathway was inhibited only by high concentrations of saliva and it was better inhibited by the midgut contents of sand flies. Neither the saliva nor the midgut contents had any effect on the avian alternative pathway. Fowl sera killed L. infantum promastigotes, even at a low concentration (2%, and the addition of L. longipalpis saliva did not protect the parasites. The high body temperature of chickens (40°C had no effect on Leishmania viability during our assays. CONCLUSION: Salivary inhibitors act in a species-specific manner. It is important to determine their effects in the natural hosts of Leishmania infantum because they act on canid and rodent complements but not on chickens (which do not harbour the parasite. Moreover, we concluded that the avian complement system is the probable mechanism through which chickens eliminate Leishmania and that their high body temperature does not influence this parasite.

MicroRNA-gene signaling pathways in pancreatic cancer

Directory of Open Access Journals (Sweden)

Alexandra Drakaki

2013-10-01

Full Text Available Pancreatic cancer is the fourth most frequent cause of cancer-related deaths and is characterized by early metastasis and pronounced resistance to chemotherapy and radiation therapy. Despite extensive esearch efforts, there is not any substantial progress regarding the identification of novel drugs against pancreatic cancer. Although the introduction of the chemotherapeutic agent gemcitabine improved clinical response, the prognosis of these patients remained extremely poor with a 5-year survival rate of 3-5%. Thus, the identification of the novel molecular pathways involved in pancreatic oncogenesis and the development of new and potent therapeutic options are highly desirable. Here, we describe how microRNAs control signaling pathways that are frequently deregulated during pancreatic oncogenesis. In addition, we provide evidence that microRNAs could be potentially used as novel pancreatic cancer therapeutics through reversal of chemotherapy and radiotherapy resistance or regulation of essential molecular pathways. Further studies should integrate the deregulated genes and microRNAs into molecular networks in order to identify the central regulators of pancreatic oncogenesis. Targeting these central regulators could lead to the development of novel targeted therapeutic approaches for pancreatic cancer patients.

Pasteurella pneumotropica evades the human complement system by acquisition of the complement regulators factor H and C4BP.

Directory of Open Access Journals (Sweden)

Alfredo Sahagún-Ruiz

Full Text Available Pasteurella pneumotropica is an opportunist Gram negative bacterium responsible for rodent pasteurellosis that affects upper respiratory, reproductive and digestive tracts of mammals. In animal care facilities the presence of P. pneumotropica causes severe to lethal infection in immunodeficient mice, being also a potential source for human contamination. Indeed, occupational exposure is one of the main causes of human infection by P. pneumotropica. The clinical presentation of the disease includes subcutaneous abscesses, respiratory tract colonization and systemic infections. Given the ability of P. pneumotropica to fully disseminate in the organism, it is quite relevant to study the role of the complement system to control the infection as well as the possible evasion mechanisms involved in bacterial survival. Here, we show for the first time that P. pneumotropica is able to survive the bactericidal activity of the human complement system. We observed that host regulatory complement C4BP and Factor H bind to the surface of P. pneumotropica, controlling the activation pathways regulating the formation and maintenance of C3-convertases. These results show that P. pneumotropica has evolved mechanisms to evade the human complement system that may increase the efficiency by which this pathogen is able to gain access to and colonize inner tissues where it may cause severe infections.

Energy subsidies in California's electricity market deregulation

International Nuclear Information System (INIS)

Ritschel, Alexander; Smestad, G.P.

2003-01-01

Deregulation and re-regulation of California's electricity market not only failed in terms of anticipated cost reductions, improved customer service and higher competition, it also led to the introduction of various additional energy subsidies. This paper analyzes California's electricity market deregulation process from a subsidy viewpoint. Under deregulation in California, investor-owned utilities were not allowed to pass their energy procurement costs fully on to their customers, and therefore subsequently, and inevitably, ran into severe financial problems. Such retail price regulation is an energy subsidy that is both economically and environmentally unfavorable, because it veils true price signals to electricity consumers and, in this way, discourages energy conservation. Other policies implemented in California that represent perverse energy subsidies are the purchase of power by the state of California, the suspension of retail competition, and the potential misuse of money from the recovery of stranded costs. Many interventions implemented by the state to smooth out the impacts of the energy crisis insulated electricity consumers from market realities, supported the existing structure of California's electricity market, which is predominantly based on fossil fuels, and suppressed market incentives to improve energy conservation

Deregulation, privatisation and marketisation of Nordic comprehensive education

DEFF Research Database (Denmark)

Dovemark, Marianne; Kosunen, Sonja; Kauko, Jaakko

2018-01-01

economy. The aim of this article is to examine education in the five Nordic countries utilising three dimensions of political change: deregulation, marketisation and privatisation. We also analyse the parallel changes in relation to segregation and differentiation in education. The analysis shows...... that the themes related to deregulation seem to show fairly similar patterns and structures in all contexts. The emerging differences were discovered mainly in the themes of marketisation and privatisation. Institutional segregation emerges in all Nordic countries to different extents along the lines...

Deregulation impacts AMR business cases

Energy Technology Data Exchange (ETDEWEB)

Wiebe, M.; Fauth, G.

2001-09-01

Meter reading strategy is being affected in fundamental ways by deregulation. For the utilities attempting to cope with meter reading unbundling, the processes, insights and general rules that had been developed prior to 2000 in the field of Automatic Meter Reading can no longer be relied upon to provide useful lessons. The fundamental impact on Automatic Meter Reading (AMR) business case drivers and the increasing complexity of building the business case model result from deregulation and unbundling. More and more, management has come to rely on rigorous business case analysis to compensate for the magnitude of AMR projects on the utility and the scarcity of financial resources. One can now expect the Chief Financial Officer and the Vice President Finance to become active players on AMR project teams in the fields of business case scrutiny and approval. Increasingly, the normal expertise of AMR personnel does not suffice to build a business case acceptable to finance. The financial and economic analysis skills required are ever more complex.

Interactions of the humoral pattern recognition molecule PTX3 with the complement system

DEFF Research Database (Denmark)

Doni, Andrea; Garlanda, Cecilia; Bottazzi, Barbara

2012-01-01

The innate immune system comprises a cellular and a humoral arm. The long pentraxin PTX3 is a fluid phase pattern recognition molecule, which acts as an essential component of the humoral arm of innate immunity. PTX3 has antibody-like properties including interactions with complement components....... PTX3 interacts with C1q, ficolin-1 and ficolin-2 as well as mannose-binding lectin, recognition molecules in the classical and lectin complement pathways. The formation of these heterocomplexes results in cooperative pathogen recognition and complement activation. Interactions with C4b binding protein...

Cell Cycle Deregulation in Ewing's Sarcoma Pathogenesis

Science.gov (United States)

Kowalewski, Ashley A.; Randall, R. Lor; Lessnick, Stephen L.

2011-01-01

Ewing's sarcoma is a highly aggressive pediatric tumor of bone that usually contains the characteristic chromosomal translocation t(11;22)(q24;q12). This translocation encodes the oncogenic fusion protein EWS/FLI, which acts as an aberrant transcription factor to deregulate target genes necessary for oncogenesis. One key feature of oncogenic transformation is dysregulation of cell cycle control. It is therefore likely that EWS/FLI and other cooperating mutations in Ewing's sarcoma modulate the cell cycle to facilitate tumorigenesis. This paper will summarize current published data associated with deregulation of the cell cycle in Ewing's sarcoma and highlight important questions that remain to be answered. PMID:21052502

Cell Cycle Deregulation in Ewing's Sarcoma Pathogenesis

Directory of Open Access Journals (Sweden)

Ashley A. Kowalewski

2011-01-01

Full Text Available Ewing's sarcoma is a highly aggressive pediatric tumor of bone that usually contains the characteristic chromosomal translocation t(11;22(q24;q12. This translocation encodes the oncogenic fusion protein EWS/FLI, which acts as an aberrant transcription factor to deregulate target genes necessary for oncogenesis. One key feature of oncogenic transformation is dysregulation of cell cycle control. It is therefore likely that EWS/FLI and other cooperating mutations in Ewing's sarcoma modulate the cell cycle to facilitate tumorigenesis. This paper will summarize current published data associated with deregulation of the cell cycle in Ewing's sarcoma and highlight important questions that remain to be answered.

The Murine Factor H-Related Protein FHR-B Promotes Complement Activation

Directory of Open Access Journals (Sweden)

Marcell Cserhalmi

2017-09-01

Full Text Available Factor H-related (FHR proteins consist of varying number of complement control protein domains that display various degrees of sequence identity to respective domains of the alternative pathway complement inhibitor factor H (FH. While such FHR proteins are described in several species, only human FHRs were functionally investigated. Their biological role is still poorly understood and in part controversial. Recent studies on some of the human FHRs strongly suggest a role for FHRs in enhancing complement activation via competing with FH for binding to certain ligands and surfaces. The aim of the current study was the functional characterization of a murine FHR, FHR-B. To this end, FHR-B was expressed in recombinant form. Recombinant FHR-B bound to human C3b and was able to compete with human FH for C3b binding. FHR-B supported the assembly of functionally active C3bBb alternative pathway C3 convertase via its interaction with C3b. This activity was confirmed by demonstrating C3 activation in murine serum. In addition, FHR-B bound to murine pentraxin 3 (PTX3, and this interaction resulted in murine C3 fragment deposition due to enhanced complement activation in mouse serum. FHR-B also induced C3 deposition on C-reactive protein, the extracellular matrix (ECM extract Matrigel, and endothelial cell-derived ECM when exposed to mouse serum. Moreover, mouse C3 deposition was strongly enhanced on necrotic Jurkat T cells and the mouse B cell line A20 by FHR-B. FHR-B also induced lysis of sheep erythrocytes when incubated in mouse serum with FHR-B added in excess. Altogether, these data demonstrate that, similar to human FHR-1 and FHR-5, mouse FHR-B modulates complement activity by promoting complement activation via interaction with C3b and via competition with murine FH.

Electricity pricing model in thermal generating stations under deregulation

International Nuclear Information System (INIS)

Reji, P.; Ashok, S.; Moideenkutty, K.M.

2007-01-01

In regulated public utilities with competitive power markets, deregulation has replaced the monopoly. Under the deregulated power market, the electricity price primarily depends on market mechanism and power demand. In this market, generators generally follow marginal pricing. Each generator fixes the electricity price based on their pricing strategy and it leads to more price volatility. This paper proposed a model to determine the electricity price considering all operational constraints of the plant and economic variables that influenced the price, for a thermal generating station under deregulation. The purpose of the model was to assist existing stations, investors in the power sector, regulatory authorities, transmission utilities, and new power generators in decision-making. The model could accommodate price volatility in the market and was based on performance incentive/penalty considering plant load factor, availability of the plant and peak/ off peak demand. The model was applied as a case study to a typical thermal utility in India to determine the electricity price. It was concluded that the case study of a thermal generating station in a deregulated environment showed that the electricity price mainly depended on the gross calorific value (GCV) of fuel, mode of operation, price of the fuel, and operating charges. 11 refs., 2 tabs., 1 fig

The Nightmare of the Leader: The Impact of Deregulation on an Oligopoly Insurance Market

OpenAIRE

Jennifer L. Wang; Larry Y. Tzeng; En-Lin Wang

2003-01-01

This paper explores the impact of deregulation of licensing on an oligopoly insurance market. We show that deregulation of licensing in a Stackelberg-type oligopoly market may not have any impact on the leader’s output if the number of firms increases but the market structure remains. On the other hand, if the market structure is reorganized because of the deregulation of licensing, the leader’s output could be significantly reduced after deregulation. By using the unique data of the insuranc...

Association of Low Ficolin-Lectin Pathway Parameters with Cardiac Syndrome X

DEFF Research Database (Denmark)

Horváth, Z; Csuka, Dorottya; Vargova, K

2016-01-01

In patients with typical angina pectoris, inducible myocardial ischaemia and macroscopically normal coronaries (cardiac syndrome X (CSX)), a significantly elevated plasma level of terminal complement complex (TCC), the common end product of complement activation, has been observed without.......003). In conclusion, in patients with typical angina and myocardial ischaemia despite macroscopically normal coronary arteries, low levels of several lectin pathway parameters were observed, indicating complement activation and consumption. Complement activation through the ficolin-lectin pathway might play a role...

Product Market Deregulation and Employment Outcomes: Evidence from the German Retail Sector

OpenAIRE

Charlotte Senftleben-König

2014-01-01

This paper investigates the short- and medium-term effects of the deregulation of shopopening hours legislation on retail employment in Germany. In 2006, the legislative competence was shifted from the federal to the state level, leading to a gradual deregulation of shop opening restrictions in most of Germany’s sixteen federal states. The paper exploits regional variation in the legislation in order to identify the effect product market deregulation has on retail employment. We find robust...

LMW-E/CDK2 Deregulates Acinar Morphogenesis, Induces Tumorigenesis, and Associates with the Activated b-Raf-ERK1/2-mTOR Pathway in Breast Cancer Patients

Science.gov (United States)

Duong, MyLinh T.; Akli, Said; Wei, Caimiao; Wingate, Hannah F.; Liu, Wenbin; Lu, Yiling; Yi, Min; Mills, Gordon B.; Hunt, Kelly K.; Keyomarsi, Khandan

2012-01-01

Elastase-mediated cleavage of cyclin E generates low molecular weight cyclin E (LMW-E) isoforms exhibiting enhanced CDK2–associated kinase activity and resistance to inhibition by CDK inhibitors p21 and p27. Approximately 27% of breast cancers express high LMW-E protein levels, which significantly correlates with poor survival. The objective of this study was to identify the signaling pathway(s) deregulated by LMW-E expression in breast cancer patients and to identify pharmaceutical agents to effectively target this pathway. Ectopic LMW-E expression in nontumorigenic human mammary epithelial cells (hMECs) was sufficient to generate xenografts with greater tumorigenic potential than full-length cyclin E, and the tumorigenicity was augmented by in vivo passaging. However, cyclin E mutants unable to interact with CDK2 protected hMECs from tumor development. When hMECs were cultured on Matrigel, LMW-E mediated aberrant acinar morphogenesis, including enlargement of acinar structures and formation of multi-acinar complexes, as denoted by reduced BIM and elevated Ki67 expression. Similarly, inducible expression of LMW-E in transgenic mice generated hyper-proliferative terminal end buds resulting in enhanced mammary tumor development. Reverse-phase protein array assay of 276 breast tumor patient samples and cells cultured on monolayer and in three-dimensional Matrigel demonstrated that, in terms of protein expression profile, hMECs cultured in Matrigel more closely resembled patient tissues than did cells cultured on monolayer. Additionally, the b-Raf-ERK1/2-mTOR pathway was activated in LMW-E–expressing patient samples, and activation of this pathway was associated with poor disease-specific survival. Combination treatment using roscovitine (CDK inhibitor) plus either rapamycin (mTOR inhibitor) or sorafenib (a pan kinase inhibitor targeting b-Raf) effectively prevented aberrant acinar formation in LMW-E–expressing cells by inducing G1/S cell cycle arrest. LMW

The deregulation of electricity and gas markets. The great economic challenges

International Nuclear Information System (INIS)

Mirabel, Francois; Guerassimoff, Gilles

2012-01-01

As the process of deregulation of electricity and gas markets started in Europe ten years ago, this book aims at recalling and describing the consequences of this evolution, notably for companies which were in a monopoly situation for electricity and gas production, transport, retailing and selling, but also in terms of new entities to be created and of entities having to give up their specialty. The author first presents the economic characteristics of gas and electricity industries in terms of infrastructures and final services, scale, coordination and size of energy networks, of existence of strong externalities in networks, of commitment in public service missions. He describes the background and implementation of this deregulation. He analyses the strategies of companies and how energy markets are controlled: strategies to mitigate competition and to strengthen their market power, firm strategies and public policies, merging strategies, strategies of competition distortion. The last chapter addresses the various priority fields of deregulation: public service missions in a deregulated environment (issues of service continuity and of affordable prices), the environmental constraint in energy market organisation (limitation of CO 2 emissions, promotion of renewable energies, and reduction of energy consumption). In conclusion, the author discusses how to conciliate deregulation and sustainable development of energy

Reactivity of alpha 1-antitrypsin mutants against proteolytic enzymes of the kallikrein-kinin, complement, and fibrinolytic systems

NARCIS (Netherlands)

Patston, P.A.; Roodi, N.; Schifferli, J.A.; Bischoff, Rainer; Courtney, M.; Schapira, M.

1990-01-01

Increased extracellular proteolysis because of unregulated activation of blood coagulation, complement, and fibrinolysis is observed in thrombosis, shock, and inflammation. In the present study, we have examined whether the plasma kallikrein-kinin system, the classical pathway of complement, and the

Ulex europaeus agglutinin II (UEA-II) is a novel, potent inhibitor of complement activation.

Science.gov (United States)

Lekowski, R; Collard, C D; Reenstra, W R; Stahl, G L

2001-02-01

Complement is an important mediator of vascular injury following oxidative stress. We recently demonstrated that complement activation following endothelial oxidative stress is mediated by mannose-binding lectin (MBL) and activation of the lectin complement pathway. Here, we investigated whether nine plant lectins which have a binding profile similar to that of MBL competitively inhibit MBL deposition and subsequent complement activation following human umbilical vein endothelial cell (HUVEC) oxidative stress. HUVEC oxidative stress (1% O(2), 24 hr) significantly increased Ulex europaeus agglutinin II (UEA-II) binding by 72 +/- 9% compared to normoxic cells. UEA-II inhibited MBL binding to HUVEC in a concentration-dependent manner following oxidative stress. Further, MBL inhibited UEA-II binding to HUVEC in a concentration-dependent manner following oxidative stress, suggesting a common ligand. UEA-II (< or = 100 micromol/L) did not attenuate the hemolytic activity, nor did it inhibit C3a des Arg formation from alternative or classical complement pathway-specific hemolytic assays. C3 deposition (measured by ELISA) following HUVEC oxidative stress was inhibited by UEA-II in a concentration-dependent manner (IC(50) = 10 pmol/L). UEA-II inhibited C3 and MBL co-localization (confocal microscopy) in a concentration-dependent manner on HUVEC following oxidative stress (IC(50) approximately 1 pmol/L). Finally, UEA-II significantly inhibited complement-dependent neutrophil chemotaxis, but failed to inhibit fMLP-mediated chemotaxis, following endothelial oxidative stress. These data demonstrate that UEA-II is a novel, potent inhibitor of human MBL deposition and complement activation following human endothelial oxidative stress.

Anopheles Midgut Epithelium Evades Human Complement Activity by Capturing Factor H from the Blood Meal

Science.gov (United States)

Khattab, Ayman; Barroso, Marta; Miettinen, Tiera; Meri, Seppo

2015-01-01

Hematophagous vectors strictly require ingesting blood from their hosts to complete their life cycles. Exposure of the alimentary canal of these vectors to the host immune effectors necessitates efficient counteractive measures by hematophagous vectors. The Anopheles mosquito transmitting the malaria parasite is an example of hematophagous vectors that within seconds can ingest human blood double its weight. The innate immune defense mechanisms, like the complement system, in the human blood should thereby immediately react against foreign cells in the mosquito midgut. A prerequisite for complement activation is that the target cells lack complement regulators on their surfaces. In this work, we analyzed whether human complement is active in the mosquito midgut, and how the mosquito midgut cells protect themselves against complement attack. We found that complement remained active for a considerable time and was able to kill microbes within the mosquito midgut. However, the Anopheles mosquito midgut cells were not injured. These cells were found to protect themselves by capturing factor H, the main soluble inhibitor of the alternative complement pathway. Factor H inhibited complement on the midgut cells by promoting inactivation of C3b to iC3b and preventing the activity of the alternative pathway amplification C3 convertase enzyme. An interference of the FH regulatory activity by monoclonal antibodies, carried to the midgut via blood, resulted in increased mosquito mortality and reduced fecundity. By using a ligand blotting assay, a putative mosquito midgut FH receptor could be detected. Thereby, we have identified a novel mechanism whereby mosquitoes can tolerate human blood. PMID:25679788

Anopheles midgut epithelium evades human complement activity by capturing factor H from the blood meal.

Directory of Open Access Journals (Sweden)

Ayman Khattab

2015-02-01

Full Text Available Hematophagous vectors strictly require ingesting blood from their hosts to complete their life cycles. Exposure of the alimentary canal of these vectors to the host immune effectors necessitates efficient counteractive measures by hematophagous vectors. The Anopheles mosquito transmitting the malaria parasite is an example of hematophagous vectors that within seconds can ingest human blood double its weight. The innate immune defense mechanisms, like the complement system, in the human blood should thereby immediately react against foreign cells in the mosquito midgut. A prerequisite for complement activation is that the target cells lack complement regulators on their surfaces. In this work, we analyzed whether human complement is active in the mosquito midgut, and how the mosquito midgut cells protect themselves against complement attack. We found that complement remained active for a considerable time and was able to kill microbes within the mosquito midgut. However, the Anopheles mosquito midgut cells were not injured. These cells were found to protect themselves by capturing factor H, the main soluble inhibitor of the alternative complement pathway. Factor H inhibited complement on the midgut cells by promoting inactivation of C3b to iC3b and preventing the activity of the alternative pathway amplification C3 convertase enzyme. An interference of the FH regulatory activity by monoclonal antibodies, carried to the midgut via blood, resulted in increased mosquito mortality and reduced fecundity. By using a ligand blotting assay, a putative mosquito midgut FH receptor could be detected. Thereby, we have identified a novel mechanism whereby mosquitoes can tolerate human blood.

Aberrant Signaling Pathways in Glioma

International Nuclear Information System (INIS)

Nakada, Mitsutoshi; Kita, Daisuke; Watanabe, Takuya; Hayashi, Yutaka; Teng, Lei; Pyko, Ilya V.; Hamada, Jun-Ichiro

2011-01-01

Glioblastoma multiforme (GBM), a WHO grade IV malignant glioma, is the most common and lethal primary brain tumor in adults; few treatments are available. Median survival rates range from 12–15 months. The biological characteristics of this tumor are exemplified by prominent proliferation, active invasiveness, and rich angiogenesis. This is mainly due to highly deregulated signaling pathways in the tumor. Studies of these signaling pathways have greatly increased our understanding of the biology and clinical behavior of GBM. An integrated view of signal transduction will provide a more useful approach in designing novel therapies for this devastating disease. In this review, we summarize the current understanding of GBM signaling pathways with a focus on potential molecular targets for anti-signaling molecular therapies

The Anticomplementary Activity of ’Fusobacterium polymorphum’ in Normal and C-4 Deficient Sources of Guinea Pig Complement.

Science.gov (United States)

1977-01-12

A complement consumption assay was used to show that the anticomplementary activity of a cell wall preparation from F. polymorphum in guinea pig complement...tests with C𔃾-deficient guinea pig sera confirmed that F. polymorphum cell walls were capable of generating alternate complement pathway activity in guinea pig sera.

Complement activation in emergency department patients with severe sepsis.

Science.gov (United States)

Younger, John G; Bracho, David O; Chung-Esaki, Hangyul M; Lee, Moonseok; Rana, Gurpreet K; Sen, Ananda; Jones, Alan E

2010-04-01

This study assessed the extent and mechanism of complement activation in community-acquired sepsis at presentation to the emergency department (ED) and following 24 hours of quantitative resuscitation. A prospective pilot study of patients with severe sepsis and healthy controls was conducted among individuals presenting to a tertiary care ED. Resuscitation, including antibiotics and therapies to normalize central venous and mean arterial pressure (MAP) and central venous oxygenation, was performed on all patients. Serum levels of Factor Bb (alternative pathway), C4d (classical and mannose-binding lectin [MBL] pathway), C3, C3a, and C5a were determined at presentation and 24 hours later among patients. Twenty patients and 10 healthy volunteer controls were enrolled. Compared to volunteers, all proteins measured were abnormally higher among septic patients (C4d 3.5-fold; Factor Bb 6.1-fold; C3 0.8-fold; C3a 11.6-fold; C5a 1.8-fold). Elevations in C5a were most strongly correlated with alternative pathway activation. Surprisingly, a slight but significant inverse relationship between illness severity (by sequential organ failure assessment [SOFA] score) and C5a levels at presentation was noted. Twenty-four hours of structured resuscitation did not, on average, affect any of the mediators studied. Patients with community-acquired sepsis have extensive complement activation, particularly of the alternative pathway, at the time of presentation that was not significantly reversed by 24 hours of aggressive resuscitation.

Trichinella spiralis Calreticulin Binds Human Complement C1q As an Immune Evasion Strategy.

Science.gov (United States)

Zhao, Limei; Shao, Shuai; Chen, Yi; Sun, Ximeng; Sun, Ran; Huang, Jingjing; Zhan, Bin; Zhu, Xinping

2017-01-01

As a multicellular parasitic nematode, Trichinella spiralis regulates host immune responses by producing a variety of immunomodulatory molecules to escape from host immune attack, but the mechanisms underlying the immune evasion are not well understood. Here, we identified that T. spiralis calreticulin ( Ts -CRT), a Ca 2+ -binding protein, facilitated T. spiralis immune evasion by interacting with the first component of human classical complement pathway, C1q. In the present study, Ts -CRT was found to be expressed on the surface of different developmental stages of T. spiralis as well as in the secreted products of adult and muscle larval worms. Functional analysis identified that Ts -CRT was able to bind to human C1q, resulting in the inhibition of C1q-initiated complement classical activation pathway reflected by reduced C4/C3 generation and C1q-dependent lysis of antibody-sensitized sheep erythrocytes. Moreover, recombinant Ts -CRT (r Ts -CRT) binding to C1q suppressed C1q-induced THP-1-derived macrophages chemotaxis and reduced monocyte-macrophages release of reactive oxygen intermediates (ROIs). Blocking Ts -CRT on the surface of newborn larvae (NBL) of T. spiralis with anti- Ts -CRT antibody increased the C1q-mediated adherence of monocyte-macrophages to larvae and impaired larval infectivity. All of these results suggest that T. spiralis -expressed Ts -CRT plays crucial roles in T. spiralis immune evasion and survival in host mostly by directly binding to host complement C1q, which not only reduces C1q-mediated activation of classical complement pathway but also inhibits the C1q-induced non-complement activation of macrophages.

Utilities' ''obligation to serve'' under deregulation

International Nuclear Information System (INIS)

Alexander, C.B.

1997-01-01

The utility no longer has protected status, and the traditional franchise concept is under attack. Exclusive rights once conveyed to the utilities are being denied and not just in the area of gas sales. Exclusive rights once conveyed to utilities will be denied in more areas. State by state, the utilities' franchise is being examined to see which, if any, of its provisions are necessary in a deregulated environment. Can the free market provide everything that's been provided for many years under monopolistic arrangements? Some of the most critical and difficult of these provisions concern the obligation to serve, which utilities, in most states, have assumed as part of their franchise agreement. Regulators, courts, utilities, marketers and others are busy sorting through these issues, but resolution could take years. The paper discusses deregulation, universal service fee, representation without taxation, suppliers and marketer restrictions

Gas directive. Which deregulation for France

International Nuclear Information System (INIS)

1999-09-01

This study deals with the following aspects of natural gas market: deregulation of the French market; status and perspectives of the gas market: overview of the gas supplies in Europe at the 2010/2015 vista; situation of regulations: status of the gas directive at the European level and impact on member states market, transposition of the gas directive in France: present day legislation, main stakes and situation of the dialogue with the actors; consequences and actors' strategy: testimony of suppliers, past and future situation, development of new activities in the gas/power industry, possible contractual evolutions, position of the supplier; testimony of clients: new suppliers, new contracts, new risks; legal stakes for the clients: impact of deregulation on contracts, future contractual organization of the market, evolution of 'take or pay' contracts, impairment of contracts obligations, negotiation of supply contracts. (J.S.)

Complement modulation of T cell immune responses during homeostasis and disease.

Science.gov (United States)

Clarke, Elizabeth V; Tenner, Andrea J

2014-11-01

The complement system is an ancient and critical effector mechanism of the innate immune system as it senses, kills, and clears infectious and/or dangerous particles and alerts the immune system to the presence of the infection and/or danger. Interestingly, an increasing number of reports have demonstrated a clear role for complement in the adaptive immune system as well. Of note, a number of recent studies have identified previously unknown roles for complement proteins, receptors, and regulators in T cell function. Here, we will review recent data demonstrating the influence of complement proteins C1q, C3b/iC3b, C3a (and C3aR), and C5a (and C5aR) and complement regulators DAF (CD55) and CD46 (MCP) on T cell function during homeostasis and disease. Although new concepts are beginning to emerge in the field of complement regulation of T cell function, future experiments should focus on whether complement is interacting directly with the T cell or is having an indirect effect on T cell function via APCs, the cytokine milieu, or downstream complement activation products. Importantly, the identification of the pivotal molecular pathways in the human systems will be beneficial in the translation of concepts derived from model systems to therapeutic targeting for treatment of human disorders. © 2014 Society for Leukocyte Biology.

Human stem cell-derived retinal epithelial cells activate complement via collectin 11 in response to stress

DEFF Research Database (Denmark)

Fanelli, Giorgia; Gonzalez-Cordero, Anai; Gardner, Peter J

2017-01-01

induced-pluripotent stem cell (iPSC)-derived RPE cells, particularly with regard to the complement pathway. We focused on collectin-11 (CL-11), a pattern recognition molecule that can trigger complement activation in renal epithelial tissue. We found evidence of constitutive and hypoxia-induced expression......, failed to activate complement. The presence of CL-11 in healthy murine and human retinal tissues confirmed the biological relevance of CL-11. Our data describe a new trigger mechanism of complement activation that could be important in disease pathogenesis and therapeutic interventions....

The Surface-Exposed Protein SntA Contributes to Complement Evasion in Zoonotic Streptococcus suis.

Science.gov (United States)

Deng, Simin; Xu, Tong; Fang, Qiong; Yu, Lei; Zhu, Jiaqi; Chen, Long; Liu, Jiahui; Zhou, Rui

2018-01-01

Streptococcus suis is an emerging zoonotic pathogen causing streptococcal toxic shock like syndrome (STSLS), meningitis, septicemia, and even sudden death in human and pigs. Serious septicemia indicates this bacterium can evade the host complement surveillance. In our previous study, a functionally unknown protein SntA of S. suis has been identified as a heme-binding protein, and contributes to virulence in pigs. SntA can interact with the host antioxidant protein AOP2 and consequently inhibit its antioxidant activity. In the present study, SntA is identified as a cell wall anchored protein that functions as an important player in S. suis complement evasion. The C3 deposition and membrane attack complex (MAC) formation on the surface of sntA -deleted mutant strain Δ sntA are demonstrated to be significantly higher than the parental strain SC-19 and the complementary strain CΔ sntA . The abilities of anti-phagocytosis, survival in blood, and in vivo colonization of Δ sntA are obviously reduced. SntA can interact with C1q and inhibit hemolytic activity via the classical pathway. Complement activation assays reveal that SntA can also directly activate classical and lectin pathways, resulting in complement consumption. These two complement evasion strategies may be crucial for the pathogenesis of this zoonotic pathogen. Concerning that SntA is a bifunctional 2',3'-cyclic nucleotide 2'-phosphodiesterase/3'-nucleotidase in many species of Gram-positive bacteria, these complement evasion strategies may have common biological significance.

Complement factor H deficiency and endocapillary glomerulonephritis due to paternal isodisomy and a novel factor H mutation

DEFF Research Database (Denmark)

Schejbel, L; Schmidt, I M; Kirchhoff, Eva Maria

2011-01-01

Complement factor H (CFH) is a regulator of the alternative complement activation pathway. Mutations in the CFH gene are associated with atypical hemolytic uremic syndrome, membranoproliferative glomerulonephritis type II and C3 glomerulonephritis. Here, we report a 6-month-old CFH-deficient child...

Deregulation of obesity-relevant genes is associated with progression in BMI and the amount of adipose tissue in pigs.

Science.gov (United States)

Mentzel, Caroline M Junker; Cardoso, Tainã Figueiredo; Pipper, Christian Bressen; Jacobsen, Mette Juul; Jørgensen, Claus Bøttcher; Cirera, Susanna; Fredholm, Merete

2018-02-01

The aim of this study was to elucidate the relative impact of three phenotypes often used to characterize obesity on perturbation of molecular pathways involved in obesity. The three obesity-related phenotypes are (1) body mass index (BMI), (2) amount of subcutaneous adipose tissue (SATa), and (3) amount of retroperitoneal adipose tissue (RPATa). Although it is generally accepted that increasing amount of RPATa is 'unhealthy', a direct comparison of the relative impact of the three obesity-related phenotypes on gene expression has, to our knowledge, not been performed previously. We have used multiple linear models to analyze altered gene expression of selected obesity-related genes in tissues collected from 19 female pigs phenotypically characterized with respect to the obesity-related phenotypes. Gene expression was assessed by high-throughput qPCR in RNA from liver, skeletal muscle and abdominal adipose tissue. The stringent statistical approach used in the study has increased the power of the analysis compared to the classical approach of analysis in divergent groups of individuals. Our approach led to the identification of key components of cellular pathways that are modulated in the three tissues in association with changes in the three obesity-relevant phenotypes (BMI, SATa and RPATa). The deregulated pathways are involved in biosynthesis and transcript regulation in adipocytes, in lipid transport, lipolysis and metabolism, and in inflammatory responses. Deregulation seemed more comprehensive in liver (23 genes) compared to abdominal adipose tissue (10 genes) and muscle (3 genes). Notably, the study supports the notion that excess amount of intra-abdominal adipose tissue is associated with a greater metabolic disease risk. Our results provide molecular support for this notion by demonstrating that increasing amount of RPATa has a higher impact on perturbation of cellular pathways influencing obesity and obesity-related metabolic traits compared to increase

Deregulation strategies for local governments and the role/opportunities for energy efficiency services in the utility industry deregulation

International Nuclear Information System (INIS)

Tseng, P.C.

1998-01-01

As the future shape of the electric utility industry continues to unfold and as retail competition becomes a reality, local governments are faced with balancing the need for: (1) economic development; (2) and to avoid the potential impact of cost-shifting among residents and businesses, while ensuring reliable and universal energy services. Furthermore, local governments need to find ways to recoup potential loss of franchise and tax revenues, to ensure fair and adequate energy-efficiency programs, and to continue other social programs for low income families. This paper will address two important issues every local government in the US are facing: (1) the development of viable deregulation strategies before, during and after the promulgation of utility deregulation; (2) opportunities for energy efficiency services in the competitive markets to serve local governments, which typically constitutes the largest market segment in utility's service territory. This paper presents issues and challenges common to all local governments. It documents strategies that several local governments are utilizing to embrace the coming electric utility restructuring and competition challenge to the benefits of their respective communities. This paper presents the results on deregulation work by the City of Portland, Oregon, Barnstable County, Massachusetts, and Montgomery County, Maryland. The research by these local governments was sponsored by the Urban Consortium Energy Task Force and Public Technology, Inc

Deregulation strategies for local governments and the role/opportunities for energy efficiency services in the utility industry deregulation

Energy Technology Data Exchange (ETDEWEB)

Tseng, P.C.

1998-07-01

As the future shape of the electric utility industry continues to unfold and as retail competition becomes a reality, local governments are faced with balancing the need for: (1) economic development; (2) and to avoid the potential impact of cost-shifting among residents and businesses, while ensuring reliable and universal energy services. Furthermore, local governments need to find ways to recoup potential loss of franchise and tax revenues, to ensure fair and adequate energy-efficiency programs, and to continue other social programs for low income families. This paper will address two important issues every local government in the US are facing: (1) the development of viable deregulation strategies before, during and after the promulgation of utility deregulation; (2) opportunities for energy efficiency services in the competitive markets to serve local governments, which typically constitutes the largest market segment in utility's service territory. This paper presents issues and challenges common to all local governments. It documents strategies that several local governments are utilizing to embrace the coming electric utility restructuring and competition challenge to the benefits of their respective communities. This paper presents the results on deregulation work by the City of Portland, Oregon, Barnstable County, Massachusetts, and Montgomery County, Maryland. The research by these local governments was sponsored by the Urban Consortium Energy Task Force and Public Technology, Inc.

Characterization and expression analysis of a complement component gene in sea cucumber ( Apostichopus japonicus)

Science.gov (United States)

Chen, Zhong; Zhou, Zunchun; Yang, Aifu; Dong, Ying; Guan, Xiaoyan; Jiang, Bei; Wang, Bai

2015-12-01

The complement system plays a crucial role in the innate immune system of animals. It can be activated by distinct yet overlapping classical, alternative and lectin pathways. In the alternative pathway, complement factor B (Bf) serves as the catalytic subunit of complement component 3 (C3) convertase, which plays the central role among three activation pathways. In this study, the Bf gene in sea cucumber ( Apostichopus japonicus), termed AjBf, was obtained by rapid amplification of cDNA ends (RACE). The full-length cDNA of AjBf was 3231 bp in length barring the poly (A) tail. It contained an open reading frame (ORF) of 2742 bp encoding 913 amino acids, a 105 bp 5'-UTR (5'-terminal untranslated region) and a 384 bp 3'-UTR. AjBf was a mosaic protein with six CCP (complement control protein) domains, a VWA (von Willebrand factor A) domain, and a serine protease domain. The deduced molecular weight of AjBf protein was 101 kDa. Quantitative real time PCR (qRT-PCR) analysis indicated that the expression level of AjBf in A. japonicus was obviously higher at larval stage than that at embryonic stage. Expression detection in different tissues showed that AjBf expressed higher in coelomocytes than in other four tissues. In addation, AjBf expression in different tissues was induced significantly after LPS or PolyI:C challenge. These results indicated that AjBf plays an important role in immune responses to pathogen infection.

The C-type lectin of the aggrecan G3 domain activates complement.

Directory of Open Access Journals (Sweden)

Camilla Melin Fürst

Full Text Available Excessive complement activation contributes to joint diseases such as rheumatoid arthritis and osteoarthritis during which cartilage proteins are fragmented and released into the synovial fluid. Some of these proteins and fragments activate complement, which may sustain inflammation. The G3 domain of large cartilage proteoglycan aggrecan interacts with other extracellular matrix proteins, fibulins and tenascins, via its C-type lectin domain (CLD and has important functions in matrix organization. Fragments containing G3 domain are released during normal aggrecan turnover, but increasingly so in disease. We now show that the aggrecan CLD part of the G3 domain activates the classical and to a lesser extent the alternative pathway of complement, via binding of C1q and C3, respectively. The complement control protein (CCP domain adjacent to the CLD showed no effect on complement initiation. The binding of C1q to G3 depended on ionic interactions and was decreased in D2267N mutant G3. However, the observed complement activation was attenuated due to binding of complement inhibitor factor H to CLD and CCP domains. This was most apparent at the level of deposition of terminal complement components. Taken together our observations indicate aggrecan CLD as one factor involved in the sustained inflammation of the joint.

Competitive positioning of power generation plants in a deregulated market

International Nuclear Information System (INIS)

Stephens, J.

1998-01-01

As industrialized countries deregulate their electric power industries, there is a fundamental shift from guaranteed cost recovery to open market competition on a deregulated grid. Utilities generally competitively bid into a power exchange where the lowest cost power providers are dispatched first. Therefore, the competitiveness of utilities determines their profitability. This commercial structure compels power generators to seek out ways of improving their equipment and plant performance. The inevitability of this trend is demonstrated by a look at the installed base in the US where the move toward deregulation is gaining momentum. More than half of the generating plants in the US are over 20 years old. The average thermal efficiency nation-wide is 33%. In contrast, contemporary coal-and gas-fired plants can operate at efficiency levels up to 45 percent and 55 to 60%, respectfully. With new facilities coming on-line, existing plants will need to make improvements to be dispatched. When deregulation fully envelopes the US market, utilities will not all fit into one pattern; their strategies and actions will depend on a multiple set of factors. Their success will be based on their ability to change landscapes from guaranteed cost recovery to competitive bidding. This paper discussers technical and commercial options available to power producers to improve their competitive positions in a deregulated market as well as software for determining the competitiveness of specific power plants and the location-based market prices of electricity. Examples of the application of alternatives will be cited along with expected payback and impact on cents per kilowatt-hour production costs

Deregulation of the electric utility industry - implications for nuclear power

International Nuclear Information System (INIS)

Fern, A.R.

2001-01-01

The deregulation movement sweeping the international electric utility community represents a dramatic shift from the traditional utility business model. This paper will focus on deregulation in the United States and the new challenges for nuclear power plant operators. An overview of the new operating models being implemented in the US will lead into a discussion on new economic and operating concerns for nuclear power plant operators. (author)

Electric deregulation in Canada

International Nuclear Information System (INIS)

Way, R.W.

1996-01-01

An outline of the electric power deregulation activities across Canada, particularly in Alberta, British Columbia, and Ontario, was presented. A central element of the restructuring is creation of a power pool which acts as an open spot market, and a transmission administrator that provides access to the generators, distribution companies, importers and exporters. Load forecasts, average daily load profile and hourly pool prices for TransAlta Corporation were presented as an example. 22 figs

Transcriptome Analysis of the Innate Immunity-Related Complement System in Spleen Tissue of Ctenopharyngodon idella Infected with Aeromonas hydrophila.

Directory of Open Access Journals (Sweden)

Yunfei Dang

Full Text Available The grass carp (Ctenopharyngodon idella is an important commercial farmed herbivorous fish species in China, but is susceptible to Aeromonas hydrophila infections. In the present study, we performed de novo RNA-Seq sequencing of spleen tissue from specimens of a disease-resistant family, which were given intra-peritoneal injections containing PBS with or without a dose of A. hydrophila. The fish were sampled from the control group at 0 h, and from the experimental group at 4, 8, 12, 24, 48 and 72 h. 122.18 million clean reads were obtained from the normalized cDNA libraries; these were assembled into 425,260 contigs and then 191,795 transcripts. Of those, 52,668 transcripts were annotated with the NCBI Nr database, and 41,347 of the annotated transcripts were assigned into 90 functional groups. 20,569 unigenes were classified into six main categories, including 38 secondary KEGG pathways. 2,992 unigenes were used in the analysis of differentially expressed genes (DEGs. 89 of the putative DEGs were related to the immune system and 41 of them were involved in the complement and coagulation cascades pathway. This study provides insights into the complement and complement-related pathways involved in innate immunity, through expression profile analysis of the genomic resources in C. idella. We conclude that complement and complement-related genes play important roles during defense against A. hydrophila infection. The immune response is activated at 4 h after the bacterial injections, indicating that the complement pathways are activated at the early stage of bacterial infection. The study has improved our understanding of the immune response mechanisms in C. idella to bacterial pathogens.

Wind power in a deregulated market

International Nuclear Information System (INIS)

Ravn, Hans F.

2000-01-01

The paper describes organisational and economic elements related to wind power in a deregulated market, it describes physical and technical characteristics of wind power and it describes how wind power is handled in daily operation as well as on the market. (author)

Deregulation of Electricity Supply Industry in Oman

Directory of Open Access Journals (Sweden)

Hamed S. Al-Maghderi

2002-06-01

Full Text Available This paper examines the opportunities available and the conditions needed for the deregulation of the Electricity Supply Industry (ESI, with particular reference to the Sultanate of Oman. The paper highlights the general issues of regulation required to encourage competition in the ESI.  After that, the discussion focuses on regulation methods in the privatized ESI by describing the regulators control through price caps setting for regulatees, the conduct regulation process, the rate of return regulation setting, and the spot market (the pool contract. Finally, the prospects of restructuring and privatizing the ESI in the Sultanate of Oman are examined by reviewing the current structure of the industry and government objectives in deregulation of the electricity sector as well as the regulation framework.

Complement-mediated neutralization of dengue virus requires mannose-binding lectin

DEFF Research Database (Denmark)

Avirutnan, Panisadee; Hauhart, Richard E; Marovich, Mary A

2011-01-01

-dependent activation of the complement cascade neutralized insect cell-derived West Nile virus (WNV) in cell culture and restricted pathogenesis in mice. Here, we investigated the antiviral activity of MBL in infection by dengue virus (DENV), a related flavivirus. Using a panel of naïve sera from mouse strains...... with lower levels. Our studies suggest that allelic variation of MBL in humans may impact complement-dependent control of DENV pathogenesis. IMPORTANCE Dengue virus (DENV) is a mosquito-transmitted virus that causes a spectrum of clinical disease in humans ranging from subclinical infection to dengue...... hemorrhagic fever and dengue shock syndrome. Four serotypes of DENV exist, and severe illness is usually associated with secondary infection by a different serotype. Here, we show that mannose-binding lectin (MBL), a pattern recognition molecule that initiates the lectin pathway of complement activation...

Deregulating the Norwegian railway: a survey of empirical experiences abroad

OpenAIRE

Røstadli, Caroline

2015-01-01

Portraying implications of deregulation, this thesis presents an extensive review of deregulation in the European railway. It targets various decision variables concerning the introduction of competitive tendering in the rail industry. This thesis attempts to take a pragmatic stand offering an improved understanding vis-à-vis on decisions that have yet to be made, concentrating on possible competition forms, auction designs and contract designs. It offers learning points and tr...

Deregulation of the electric utility industry - implications for nuclear power

International Nuclear Information System (INIS)

Fern, A.Rose

2000-01-01

The deregulation movement sweeping the international electric utility community represents a dramatic shift om the traditional business model of utilities. This paper will focus on deregulation in thc United States and the new challenges for nuclear power plant operators. An overview of the new operating models being implemented in the US will lead into a discussion on new economic and operating concerns for nuclear power plant operators. (author)

Electricity market deregulation and its impact on the nuclear industry

International Nuclear Information System (INIS)

Jung, Y.E.; Alfors, G.

2000-01-01

Electricity has traditionally been supplied in OECD countries by state-owned facilities, or state-protected monopolies with regulated pricing. More recently, however, several countries have deregulated their electricity markets, thus opening the door to competitive supply and pricing. Deregulation of electricity markets is a trend that is expected to be followed by many countries, and can have a significant impact on the future of nuclear power programmes. (authors)

Developing products and services for a deregulated market while regulated

International Nuclear Information System (INIS)

Haites, E.F.

1997-01-01

Products and services developed for a deregulated electric power industry were discussed. The wide-ranging discussion covered products created by unbundling existing services, new products and services related to energy use, products created by expansion into communications services, and the pricing of products and services. In addition to products and services, the discussion also covered strategies for a deregulated market and the challenges of raising equity capital in a regulated environment

Deregulation, a challenge for regulators

International Nuclear Information System (INIS)

Alonso, Augustin

2001-01-01

Deregulation and competitiveness in the electricity market invites the plant owner/operator to reduce operating cost with a potential reduction in maintenance, degradation of investment in safety, reduction of operating staff and a downgrading in research and development. On the other side, deregulation and competitiveness brings the social and industrial benefit of reducing the electricity cost. Regulatory organisations have to watch that the safety level of the plant does not go beyond the established level, while recognising the benefits of the new situation; therefore they have the moral responsibility of regulating nuclear energy effectively and efficiently and in eliminating unnecessary regulatory burdens. Regulation has evolved with time and in accordance with the knowledge gained from research and the analysis of operating experience. The knowledge gained has made it possible to follow the path of other modern advanced technologies, where risk is quantified and the system approved when the risk becomes lower than an accepted level. The regulatory use of this advanced tool is being now developed by the most advanced regulatory organisations, under the name of risk informed regulation, where the reference level is the expected frequency of core damage. Deregulation and competitiveness will not change the basis of the already well established procedure to verify compliance. Nevertheless, the contents of Safety Analysis Reports and other regulatory documents, such as Technical Specifications for Operation, offer room for improvement in the sense of being more to the roots of the matter and becoming more efficient tools in the verification process. The contents of these documents have been evolving along the time and they have become unnecessary voluminous and rather burdensome. Much work has been done to improve the efficiency of regulatory inspections by concentrating on basic aspects. As a partial application of the already mentioned risk-informed regulation

Why Shops Close Again : An Evolutionary Perspective on the Deregulation of Shopping Hours

OpenAIRE

Kosfeld, M.

1999-01-01

This paper introduces a new perspective on the deregulation of shopping hours based on ideas from evolutionary game theory. We study a retail economy where shopping hours have been deregulated recently. It is argued that first, the deregulation leads to a coordination problem between store owners and customers, and second, the ‘solution’ to this problem depends on the specific cost structure of stores and the preferences of customers. In particular, it may happen that, even if extended shoppi...

Industrial consumers and electricity sector deregulation

International Nuclear Information System (INIS)

Jukic, A.

1999-01-01

The paper presents the electricity sector deregulation from the point of view of major industrial consumers (MIC). Possibilities and limitations of MIC's impact on the introduction and development of an open power market in some European countries, the USA and Croatia are discussed. (author)

Regulatory Assessment of the Effects of Economic Deregulation of the Nuclear Industry

International Nuclear Information System (INIS)

2002-11-01

The European Commission Nuclear Regulators Working Group (NRWG) appointed a Task Force (TF) to develop a common view among European regulators on the assessment of typical safety consequences resulting from economic pressure on operators as a result of deregulation of electricity markets. Although the report seems to imply that there are only negative aspects of deregulation, this is not the case. As the focus of the TF has been potential safety consequences we have not dealt with potential positive effects of deregulation. To provide a general background to the analyses of the safety consequences, the TF undertook a survey of the current situation within the EU and candidate countries on aspects of economic deregulation of the countries nuclear industry and the experiences so far of regulating these issues. Answers were submitted in of July 2001. 13 NRWG members with nuclear power plants took part in the survey. (author)

Integrated analysis of breast cancer cell lines reveals unique signaling pathways

Energy Technology Data Exchange (ETDEWEB)

Heiser, Laura M.; Wang, Nicholas J.; Talcott, Carolyn L.; Laderoute, Keith R.; Knapp, Merrill; Guan, Yinghui; Hu, Zhi; Ziyad, Safiyyah; Weber, Barbara L.; Laquerre, Sylvie; Jackson, Jeffrey R.; Wooster, Richard F.; Kuo, Wen-Lin; Gray, Joe W.; Spellman, Paul T.

2009-03-31

Cancer is a heterogeneous disease resulting from the accumulation of genetic defects that negatively impact control of cell division, motility, adhesion and apoptosis. Deregulation in signaling along the EGFR-MAPK pathway is common in breast cancer, though the manner in which deregulation occurs varies between both individuals and cancer subtypes. We were interested in identifying subnetworks within the EGFR-MAPK pathway that are similarly deregulated across subsets of breast cancers. To that end, we mapped genomic, transcriptional and proteomic profiles for 30 breast cancer cell lines onto a curated Pathway Logic symbolic systems model of EGFR-MEK signaling. This model was comprised of 539 molecular states and 396 rules governing signaling between active states. We analyzed these models and identified several subtype specific subnetworks, including one that suggested PAK1 is particularly important in regulating the MAPK cascade when it is over-expressed. We hypothesized that PAK1 overexpressing cell lines would have increased sensitivity to MEK inhibitors. We tested this experimentally by measuring quantitative responses of 20 breast cancer cell lines to three MEK inhibitors. We found that PAK1 over-expressing luminal breast cancer cell lines are significantly more sensitive to MEK inhibition as compared to those that express PAK1 at low levels. This indicates that PAK1 over-expression may be a useful clinical marker to identify patient populations that may be sensitive to MEK inhibitors. All together, our results support the utility of symbolic system biology models for identification of therapeutic approaches that will be effective against breast cancer subsets.

Integrated analysis of breast cancer cell lines reveals unique signaling pathways.

Science.gov (United States)

Heiser, Laura M; Wang, Nicholas J; Talcott, Carolyn L; Laderoute, Keith R; Knapp, Merrill; Guan, Yinghui; Hu, Zhi; Ziyad, Safiyyah; Weber, Barbara L; Laquerre, Sylvie; Jackson, Jeffrey R; Wooster, Richard F; Kuo, Wen Lin; Gray, Joe W; Spellman, Paul T

2009-01-01

Cancer is a heterogeneous disease resulting from the accumulation of genetic defects that negatively impact control of cell division, motility, adhesion and apoptosis. Deregulation in signaling along the EgfR-MAPK pathway is common in breast cancer, though the manner in which deregulation occurs varies between both individuals and cancer subtypes. We were interested in identifying subnetworks within the EgfR-MAPK pathway that are similarly deregulated across subsets of breast cancers. To that end, we mapped genomic, transcriptional and proteomic profiles for 30 breast cancer cell lines onto a curated Pathway Logic symbolic systems model of EgfR-MAPK signaling. This model was composed of 539 molecular states and 396 rules governing signaling between active states. We analyzed these models and identified several subtype-specific subnetworks, including one that suggested Pak1 is particularly important in regulating the MAPK cascade when it is over-expressed. We hypothesized that Pak1 over-expressing cell lines would have increased sensitivity to Mek inhibitors. We tested this experimentally by measuring quantitative responses of 20 breast cancer cell lines to three Mek inhibitors. We found that Pak1 over-expressing luminal breast cancer cell lines are significantly more sensitive to Mek inhibition compared to those that express Pak1 at low levels. This indicates that Pak1 over-expression may be a useful clinical marker to identify patient populations that may be sensitive to Mek inhibitors. All together, our results support the utility of symbolic system biology models for identification of therapeutic approaches that will be effective against breast cancer subsets.

PO-20 - Crosstalk between the lectin pathway and haemostasis in patients with pulmonary cancer

DEFF Research Database (Denmark)

Larsen, J B; Christensen, T D; Hvas, C L

2016-01-01

INTRODUCTION: Recent research has focused on the complement system in cancer, including the lectin pathway of complement activation. Mannose-binding lectin (MBL), a key activator of the lectin pathway, can bind to tumor cell surfaces in vitro, and lectin pathway activation is increased in several...

Characterization of the third component of complement (C3) after activation by cigarette smoke

International Nuclear Information System (INIS)

Kew, R.R.; Ghebrehiwet, B.; Janoff, A.

1987-01-01

Activation of lung complement by tobacco smoke may be an important pathogenetic factor in the development of pulmonary emphysema in smokers. We previously showed that cigarette smoke can modify C3 and activate the alternative pathway of complement in vitro. However, the mechanism of C3 activation was not fully delineated in these earlier studies. In the present report, we show that smoke-treated C3 induces cleavage of the alternative pathway protein, Factor B, when added to serum containing Mg-EGTA. This effect of cigarette smoke is specific for C3 since smoke-treated C4, when added to Mg-EGTA-treated serum, fails to activate the alternative pathway and fails to induce Factor B cleavage. Smoke-modified C3 no longer binds significant amounts of [ 14 C]methylamine (as does native C3), and relatively little [ 14 C]methylamine is incorporated into its alpha-chain. Thus, prior internal thiolester bond cleavage appears to have occurred in C3 activated by cigarette smoke. Cigarette smoke components also induce formation of noncovalently associated, soluble C3 multimers, with a Mr ranging from 1 to 10 million. However, prior cleavage of the thiolester bond in C3 with methylamine prevents the subsequent formation of these smoke-induced aggregates. These data indicate that cigarette smoke activates the alternative pathway of complement by specifically modifying C3 and that these modifications include cleavage of the thiolester bond in C3 and formation of noncovalently linked C3 multimers

DAIRY DEREGULATION AND LOW-INPUT DAIRY PRODUCTION: A BIOECONOMIC EVALUATION

OpenAIRE

Tozer, Peter R.; Huffaker, Ray G.

1999-01-01

Deregulation of the Australian dairy industry could affect the utilization of resources by milk producers and the profitability of dairy production. In this study we examine the feed mix that dairy producers use, both pastures and supplements, under partial and total deregulation. We are particularly interested in the interaction of pasture utilization and farm profitability. The results of this research demonstrate that profitable low-input dairy is constrained by the most limiting resource,...

Reactor decommissioning in a deregulated market

International Nuclear Information System (INIS)

Beverridge, George; Cooper, T.

2002-01-01

Full text: Deregulation of the electricity markets in North America and Western Europe has had many profound effects on the electric utilities and the nuclear industry. Deregulation has led to cost transparency, increased competition, and a drive by the utilities to reduce costs in order to maintain market share and margins. In the context of this more competitive and dynamic market having a clear picture of decommissioning liabilities and their successful discharge has a material impact on the financial performance of a utility. This paper will summarise BNFL Environmental Services' experience with regard to its experience in both the planning and implementation phases of a reactor decommissioning project. In particular it will demonstrate how commercial projects in crucial areas of strategy development, project implementation and site restoration, can be combined with an approach that is both commercial and innovative to reduce the risks to a utility. This paper sets out to demonstrate this viewpoint. (author)

Transmission management in the deregulated environment

International Nuclear Information System (INIS)

Christie, R.D.; Wollenberg, B.F.; Wangensteen, I.

2000-01-01

Three very different methods of accomplishing the same task--managing the operation of the transmission system in the deregulated power system operating environment--have been implemented as deregulated market structures have been created around the world. They are first, the optimal power flow (OPF) model found in various implementations in the United Kingdom, parts of the United States, and in Australia and New Zealand. Second, the point tariff, price area congestion control model used in the Nordpool market area in Norway and Sweden. Third, the US transaction-based model. All are pragmatic solutions implemented in advance of complete theoretical understanding. Each has strengths and flaws, and there are some surprising inter-relationships. Each maintains power system security but differs in its impact on the economics of the energy market. No clearly superior method has so far emerged. In the future, methods of combining decentralized market solutions with operational use of optimal power flow may provide better solutions to existing and emerging problems

Effects of the Deregulation on the Concentration of the Brazilian Air Transportation Industry

Science.gov (United States)

Guterres, Marcelo Xavier; Muller, Carlos

2003-01-01

This paper addresses the effects of the deregulation of the Brazilian air transportation industry in terms of the concentration of the market. We will show some metrics that are commonly used to study the concentration of the industry. This paper uses the Herfindhal- Hirschman Index. This index tends to zero in the competitive scenario, with a large number of small firms, and to one in case of a monopolistic scenario. The paper analyses the dynamics of the concentration of the Brazilian domestic air transportation market, in order to evaluate the effects of deregulation. We conclude that the Brazilian market presents oligopoly characteristics and aspects in its current structure that maintain the market concentrated in spite of the Deregulation measures adopted by the aeronautical authority. Keywords: Herfindhal-Hirschman Index, concentration, Deregulation

Anti-complement activity in the saliva of phlebotomine sand flies and other haematophagous insects.

Science.gov (United States)

Cavalcante, R R; Pereira, M H; Gontijo, N F

2003-07-01

The saliva of haematophagous insects has a series of pharmacological activities which may favour blood feeding. In the present study, an inhibitory effect on the complement system was observed in salivary extracts obtained from the phlebotomine sand flies Lutzomyia longipalpis and Lu. migonei. Saliva from Lu. longipalpis was capable of inhibiting both the classical and alternative pathways, while that from Lu. migonei acted only on the former. Other haematophagous insect species were screened for inhibition of the classical pathway. The triatomine bugs Panstrongylus megistus, Triatoma brasiliensis and Rhodnius prolixus were also able to inhibit the classical pathway whereas the mosquito Aedes aegyti and flea Ctenocephalides felis were not. The activity of Lu. longipalpis saliva on the classical pathway was partially characterized. The inhibitor is a protein of Mr 10000-30000 Da, which is very resistant to denaturation by heat. The inhibition of the complement system by phlebotomine sand flies may have a role in the transmission of Leishmania to the vertebrate hosts. The inhibitor molecule is thus a promising component of a vaccine to target salivary immunomodulators.

Heparin-coated cardiopulmonary bypass circuits selectively deplete the pattern recognition molecule ficolin-2 of the lectin complement pathway in vivo

DEFF Research Database (Denmark)

Hein, Estrid; Munthe-Fog, L; Thiara, A S

2015-01-01

of infections. Thus, we investigated the biocompatibility of the recognition molecules of the lectin pathway in two different types of cardiopulmonary bypass circuits. Bloods were drawn at five time-points before, during and postoperatively from 30 patients undergoing elective cardiac surgery. Patients were...... randomized into two groups using different coatings of cardiopulmonary bypass circuits, Phisio® (phosphorylcholine polymer coating) and Bioline® (albumin-heparin coating). Concentrations of MBL, ficolin-1, -2 and -3 and soluble C3a and terminal complement complex (TCC) in plasma samples were measured......-2 was depleted from plasma during cardiac surgery when using heparin-coated bypass circuits and did not reach baseline level 24 h postoperation. These findings may have implications for the postoperative susceptibility to infections in patients undergoing extracorporeal circulation procedures....

Power system deregulation and the Balkan countries

International Nuclear Information System (INIS)

Glamochanin, Vlastimir; Stojkovska, Biljana; Cherepnalkoski, Trajche

2001-01-01

The aim of the paper is to show the current state and planned activities of the Power System deregulation and privatization in the following Balkan countries: Macedonia, Romania, Bulgaria, Yugoslavia, Greece, Croatia, Slovenia and Turkey

Natural gas retailing: writing the last chapter of natural gas deregulation

International Nuclear Information System (INIS)

Bjerkelund, T.

1995-01-01

Under the A greement on Natural Gas Markets and Prices of October 1985, the Canadian federal government agreed to deregulate the price of natural gas and to allow a competitive gas market to develop. Several beneficial changes that have occurred as a result of the deregulation were described, including the Industrial Gas Users Association's (IGUA) view on the marketing and sale of natural gas by local gas distributor's (LDC) and the sale within the LDC franchise. IGUA's support for the separation between LDC distribution and LDC sales and marketing activities as the last step in deregulation process, was explained. Several arguments for the opposing view were also discussed. Recommendations were made for effective separation of LDC distribution and LDC sales/marketing activities

Incident microalbuminuria and complement factor mannan-binding lectin-associated protein 19 in people with newly diagnosed type 1 diabetes

DEFF Research Database (Denmark)

Ostergaard, J A; Thiel, S; Hoffmann-Petersen, I T

2017-01-01

BACKGROUND: Evidence links the lectin pathway of complement activation to diabetic kidney disease. Upon carbohydrate-recognition by pattern-recognition molecules, e.g., mannan-binding lectin (MBL), the MBL-associated serine protease (MASP-2) is activated and initiates the complement cascade. The ...

Deregulation of natural gas in Georgia

International Nuclear Information System (INIS)

Wise, S.

2002-01-01

The Natural Gas Competition and Deregulation Act of 1997 in Georgia is discussed. New legislation passed the Natural Gas Consumer Relief Act in 2002 legislative session to provide additional protection and increase competition. This Act and its impacts are discussed in detail. Additional commission responsibilities are summarized. (R.P.)

IMPACT OF DEREGULATION ON FINANCIAL SECTOR ...

African Journals Online (AJOL)

and the efficiency in the allocation of the society's resources, which were not ... financial system so as to make the system operate on the basis of the market ..... cases, the null hypothesis that financial sector deregulation does not granger .... Financial Sector Development and Growth: Evidence from Malaysia, Brookings.

A tick mannose-binding lectin inhibits the vertebrate complement cascade to enhance transmission of the Lyme disease agent

OpenAIRE

Schuijt, Tim J.; Coumou, Jeroen; Narasimhan, Sukanya; Dai, Jianfeng; DePonte, Kathleen; Wouters, Diana; Brouwer, Mieke; Oei, Anneke; Roelofs, Joris J.T.H.; van Dam, Alje P.; van der Poll, Tom; van ’t Veer, Cornelis; Hovius, Joppe W.; Fikrig, Erol

2011-01-01

The Lyme disease agent, Borrelia burgdorferi, is primarily transmitted to vertebrates by Ixodes ticks. The classical and alternative complement pathways are important in Borrelia eradication by the vertebrate host. We recently identified a tick salivary protein, designated P8 that reduced complement-mediated killing of Borrelia. We now discover that P8 interferes with the human lectin complement cascade resulting in impaired neutrophil phagocytosis and chemotaxis, and diminished Borrelia lysi...

Lectin Complement Pathway Proteins in Healthy Individuals

DEFF Research Database (Denmark)

Troldborg, Anne; Hansen, Annette Gudmann; Hansen, Søren W K

2017-01-01

, it is pivotal to know the normal. Our aim was to describe the concentrations of the eleven known proteins of the lectin pathway in serum and plasma and to uncover possible gender differences, age and diurnal variations, which must be taken into account for investigations in different cohorts. We examined...... morning to the middle of night. There were gender differences for most proteins, whereas age did not seem to influence concentration. The present study underlines the necessity of considering which material to use, correct matching and a trial design that takes the nature of the protein into account...

The role of complement in cnidarian-dinoflagellate symbiosis and immune challenge in the sea anemone Aiptasia pallida

Directory of Open Access Journals (Sweden)

Angela ePoole

2016-04-01

Full Text Available The complement system is an innate immune pathway that in vertebrates, is responsible for initial recognition and ultimately phagocytosis and destruction of microbes. Several complement molecules including C3, Factor B, and mannose binding lectin associated serine proteases (MASP have been characterized in invertebrates and while most studies have focused on their conserved role in defense against pathogens, little is known about their role in managing beneficial microbes. The purpose of this study was to (1 characterize complement pathway genes in the symbiotic sea anemone A. pallida, (2 investigate the evolution of complement genes in invertebrates, and (3 examine the potential dual role of complement genes Factor B and MASP in the onset and maintenance of cnidarian-dinoflagellate symbiosis and immune challenge using qPCR based studies. The results demonstrate that A. pallida has multiple Factor B genes (Ap_Bf-1, Ap_Bf-2a, and Ap_Bf-2b and one MASP gene (Ap_MASP. Phylogenetic analysis indicates that the evolutionary history of complement genes is complex, and there have been many gene duplications or gene loss events, even within members of the same phylum. Gene expression analyses revealed a potential role for complement in both onset and maintenance of cnidarian-dinoflagellate symbiosis and immune challenge. Specifically, Ap_Bf-1 and Ap_MASP are significantly upregulated in the light at the onset of symbiosis and in response to challenge with the pathogen Serratia marcescens suggesting that they play a role in the initial recognition of both beneficial and harmful microbes. Ap_Bf-2b in contrast was generally downregulated during the onset and maintenance of symbiosis and in response to challenge with S. marcescens. Therefore the exact role of Ap_Bf-2b in response to microbes remains unclear, but the results suggests that the presence of microbes leads to repressed expression. Together these results indicate functional divergence between Ap

The effect of airline deregulation on automobile fatalities.

Science.gov (United States)

Bylow, L F; Savage, I

1991-10-01

This paper attempts to quantify the effects of airline deregulation in the United States on intercity automobile travel and consequently on the number of highway fatalities. A demand model is constructed for auto travel, which includes variables representing the price and availability of air service. A reduced form model of the airline market is then estimated. Finding that deregulation has decreased airfares and increased flights, it is estimated that auto travel has been reduced by 2.2% per year on average. Given assumptions on the characteristics of drivers switching modes and the types of roads they drove on, the number of automobile fatalities averted since 1978 is estimated to be in the range 200-300 per year.

Overview of the developments in the domestic airline industry in South Africa since market deregulation

Directory of Open Access Journals (Sweden)

Rose Luke

2013-11-01

Full Text Available Deregulation or liberalisation of air transport has had major global impacts on the domestic air transport markets, with effects ranging from stimulation to changes in the structure and functioning of these markets. In South Africa, deregulation has had wide-reaching effects on the domestic market. The purpose of this article was to investigate the current domestic air transport market. A literature review was performed to examine the effects of deregulation in other domestic air transport markets around the world. This was followed by a review of the South African domestic air transport market prior to deregulation in order to determine the changes that were made following deregulation. The ten-year period immediately following deregulation was also examined; this period was characterised by relatively large numbers of market entries and exits. A database was obtained from the Airports Company South Africa; air traffic movements, passenger numbers and load factors were evaluated. The study showed that the market is still characterised by regular market entries and exits. Also that the entry of the low-cost carriers has stimulated the market, resulting in increased air traffic movements, higher passenger numbers, higher load factors in general and the opening of a secondary airport in Gauteng, Lanseria International. Deregulation and, more specifically, the entry of the low-cost carriers has resulted in structural changes in the market and more choice for passengers.

University Staff’s Perception of Deregulation on Higher Education in Nigeria

Directory of Open Access Journals (Sweden)

Adebayo Florence Aduke

2014-04-01

Full Text Available The study investigated the university staff’s perception on deregulation of higher education in Nigeria. Descriptive research of the survey type was used for the study. The population comprised all the university staff of universities in Ekiti and Ondo states, Nigeria. Simple random sampling technique was used to select 700 academic and non-academic staff from the Federal and State universities in Ekiti and Ondo states. Research instrument designated University Staff Perception of Deregulation on Higher Education (USPDHE was used in collecting data. The questionnaire was subjected to face and content validity. The reliability co-efficient of the instrument was 0.75. The results showed that deregulation improved academic standard of the universities except in the areas of curriculum innovation and collaborative research and does not guarantee job security nor improve staff development and equity in salary structure but it contributed to managerial effectiveness, efficiency and accountability, It also showed that students were affected in the area of access to higher education, class structure, admission choice and exploitation by the institutions. It equally showed that deregulation is not improving the funding of higher institutions in Nigeria instead it throws the institution into dilemma of sourcing for fund. Some of the recommendations are: using management strategies at the institutional level, autonomy should use management strategies that emphasize improved standards in terms of improved curricula, and academic excellence by all and sundry within the system. Also, to have the full gains of deregulation, climate of academic integrity should be enshrined in the operation of the university system.

Accounting for gas in a de-regulated environment

International Nuclear Information System (INIS)

Zawalykut, P.M.

1992-01-01

Since the natural gas industry was deregulated, the method of buying, selling and moving gas has changed significantly. Post-deregulation, the pipeline company moves the gas but does not acquire ownership. The full impact of deregulation is seen in opening up the market for buying and selling gas. Tracking of gas has become critical. The service customer is now buying and moving gas. The end-use customer nominates to the distribution company a quantity of gas to be transported. Responsibility is placed on the customer to estimate loads as accurately as possible to avoid possible charges. The distribution company passes the end-user nomination to the upstream transmission company, which in turn passes it along, a process that is repeated until the nomination reaches the production company. Authorizations for gas follow a similar path. The major difference between sales and service gas is the accounting and tracking. As the customer will not consume the exact amount nominated, there will be an imblance between what was nominated and metered. There will also be imbalances between what the producer places into the pipeline and what was nominated. These processes can cause administrative problems, and many customers are moving from sales to service

Choice of electricity provider in California after deregulation

Science.gov (United States)

Keanini, Rasa Ilze

Surveys often ask consumers how much they are willing to pay for certain goods and services, without requiring the consumer to actually pay for the good or service. Such surveys, termed stated preference studies, find that consumers value renewable electricity. This result is in contrast to actual experiences in recently deregulated electricity markets in several states, including California. When given the opportunity to choose in California, only one to two percent of the population opted for renewable electricity products. This dissertation used data from residential customers who chose an alternative electricity product in California's deregulated electricity market to determine the value placed on the renewable attribute of electricity products. This dissertation begins by taking a historical look at the electricity market of the nation and specifically California. From 1998 through 2001, California's electricity market was deregulated to include retail competition. This dissertation used data from electric service providers to reveal the factors influencing residential customer's choice of electricity product. Discrete choice models were used to determine the factors influencing electricity product choice. The results indicated that both price and renewable content had an effect on choice of product. Additionally, a more complicated model jointly estimating the discrete choice of electricity product with the continuous choice of electricity consumption (kWh) was specified and estimated.

Triatoma infestans Calreticulin: Gene Cloning and Expression of a Main Domain That Interacts with the Host Complement System.

Science.gov (United States)

Weinberger, Katherine; Collazo, Norberto; Aguillón, Juan Carlos; Molina, María Carmen; Rosas, Carlos; Peña, Jaime; Pizarro, Javier; Maldonado, Ismael; Cattan, Pedro E; Apt, Werner; Ferreira, Arturo

2017-02-08

Triatoma infestans is an important hematophagous vector of Chagas disease, a neglected chronic illness affecting approximately 6 million people in Latin America. Hematophagous insects possess several molecules in their saliva that counteract host defensive responses. Calreticulin (CRT), a multifunctional protein secreted in saliva, contributes to the feeding process in some insects. Human CRT (HuCRT) and Trypanosoma cruzi CRT (TcCRT) inhibit the classical pathway of complement activation, mainly by interacting through their central S domain with complement component C1. In previous studies, we have detected CRT in salivary gland extracts from T. infestans We have called this molecule TiCRT. Given that the S domain is responsible for C1 binding, we have tested its role in the classical pathway of complement activation in vertebrate blood. We have cloned and characterized the complete nucleotide sequence of CRT from T. infestans , and expressed its S domain. As expected, this S domain binds to human C1 and, as a consequence, it inhibits the classical pathway of complement, at its earliest stage of activation, namely the generation of C4b. Possibly, the presence of TiCRT in the salivary gland represents an evolutionary adaptation in hematophagous insects to control a potential activation of complement proteins, present in the massive blood meal that they ingest, with deleterious consequences at least on the anterior digestive tract of these insects. © The American Society of Tropical Medicine and Hygiene.

Complement-mediated killing of Borrelia burgdorferi by nonimmune sera from sika deer.

Science.gov (United States)

Nelson, D R; Rooney, S; Miller, N J; Mather, T N

2000-12-01

Various species of cervid deer are the preferred hosts for adult, black-legged ticks (Ixodes scapularis and Ixodes pacificus) in the United States. Although frequently exposed to the agent of Lyme disease (Borrelia burgdorferi), these animals, for the most part, are incompetent as transmission reservoirs. We examined the borreliacidal activity of normal and B. burgdorferi-immune sera from sika deer (Cervus nippon) maintained in a laboratory setting and compared it to that of similar sera from reservoir-competent mice and rabbits. All normal deer sera (NDS) tested killed > 90% of B. burgdorferi cells. In contrast, normal mouse and rabbit sera killed feeding exhibited IFA titers of 1:256, whereas sera from mice and rabbits similarly exposed had titers of > 1:1,024. Heat treatment (56 C, 30 min) of NDS reduced borreliacidal activity, with complement-mediated killing. The chelators EGTA and EDTA were used to block the classical or both the classical and alternative complement pathways, respectively. Addition of 10 mM EGTA to NDS had a negligible effect on borreliacidal activity, with > 90% of the cells killed. Addition of 10 mM EDTA reduced the killing to approximately 30%, whereas the addition of Mg2+ (10 mM) restored borreliacidal activity to NDS. The addition of zymosan A, an activator of the alternative pathway, increased the survival of B. burgdorferi cells to approximately 80% in NDS. These data suggest that the alternative complement activation pathway plays a major role in the borreliacidal activity of NDS. Additionally, 10 mM EGTA had almost no effect on the killing activity of B. burgdorferi-exposed deer sera, suggesting that the classical pathway is not involved in Borrelia killing, even in sera from B. burgdorferi-exposed deer.

Buying and selling green: deregulation and green power marketing

International Nuclear Information System (INIS)

Evans, Andrew

2000-01-01

This article discusses the increasing trend towards deregulation of electricity markets, and the driving forces for liberalisation in the EU and North America. The use of green tariffs offered by utilities to differentiate themselves from competitors and to gain and keep customers is reported, and the situation with regard to green energy within the deregulated electricity markets in Australia, the EU, Denmark, Finland, Germany, the Netherlands, Portugal, Sweden, the UK, Canada and the USA is outlined. Customers switching as a result of green tariffs, the growing role of renewables, and opportunities for the promotion of green tariffs are discussed. (UK)

Dynamics of human complement-mediated killing of Klebsiella pneumoniae.

Science.gov (United States)

Nypaver, Christina M; Thornton, Margaret M; Yin, Suellen M; Bracho, David O; Nelson, Patrick W; Jones, Alan E; Bortz, David M; Younger, John G

2010-11-01

With an in vitro system that used a luminescent strain of Klebsiella pneumoniae to assess bacterial metabolic activity in near-real-time, we investigated the dynamics of complement-mediated attack in healthy individuals and in patients presenting to the emergency department with community-acquired severe sepsis. A novel mathematical/statistical model was developed to simplify light output trajectories over time into two fitted parameters, the rate of complement activation and the delay from activation to the onset of killing. Using Factor B-depleted serum, the alternative pathway was found to be the primary bactericidal effector: In the absence of B, C3 opsonization as measured by flow cytometry did not progress and bacteria proliferated near exponentially. Defects in bacterial killing were easily demonstrable in patients with severe sepsis compared with healthy volunteers. In most patients with sepsis, the rate of activation was higher than in normal subjects but was associated with a prolonged delay between activation and bacterial killing (P < 0.05 for both). Theoretical modeling suggested that this combination of accentuated but delayed function should allow successful bacterial killing but with significantly greater complement activation. The use of luminescent bacteria allowed for the development of a novel and powerful tool for assessing complement immunology for the purposes of mechanistic study and patient evaluation.

Energy deregulation: lessons from the American experience

International Nuclear Information System (INIS)

Chiam, L.

1997-01-01

This article presents a brief history of US energy regulation, considers some of the important issues arising from the US experience and finally, suggests some lessons which Australia might draw from the US deregulation of energy industries. 5 refs

Human Properdin Opsonizes Nanoparticles and Triggers a Potent Pro-inflammatory Response by Macrophages without Involving Complement Activation

Science.gov (United States)

Kouser, Lubna; Paudyal, Basudev; Kaur, Anuvinder; Stenbeck, Gudrun; Jones, Lucy A.; Abozaid, Suhair M.; Stover, Cordula M.; Flahaut, Emmanuel; Sim, Robert B.; Kishore, Uday

2018-01-01

Development of nanoparticles as tissue-specific drug delivery platforms can be considerably influenced by the complement system because of their inherent pro-inflammatory and tumorigenic consequences. The complement activation pathways, and its recognition subcomponents, can modulate clearance of the nanoparticles and subsequent inflammatory response and thus alter the intended translational applications. Here, we report, for the first time, that human properdin, an upregulator of the complement alternative pathway, can opsonize functionalized carbon nanotubes (CNTs) via its thrombospondin type I repeat (TSR) 4 and 5. Binding of properdin and TSR4+5 is likely to involve charge pattern/polarity recognition of the CNT surface since both carboxymethyl cellulose-coated carbon nanotubes (CMC-CNT) and oxidized (Ox-CNT) bound these proteins well. Properdin enhanced the uptake of CMC-CNTs by a macrophage cell line, THP-1, mounting a robust pro-inflammatory immune response, as revealed by qRT-PCR, multiplex cytokine array, and NF-κB nuclear translocation analyses. Properdin can be locally synthesized by immune cells in an inflammatory microenvironment, and thus, its interaction with nanoparticles is of considerable importance. In addition, recombinant TSR4+5 coated on the CMC-CNTs inhibited complement consumption by CMC-CNTs, suggesting that nanoparticle decoration with TSR4+5, can be potentially used as a complement inhibitor in a number of pathological contexts arising due to exaggerated complement activation. PMID:29483907

Transposable Elements in Human Cancer: Causes and Consequences of Deregulation

Science.gov (United States)

Anwar, Sumadi Lukman; Wulaningsih, Wahyu; Lehmann, Ulrich

2017-01-01

Transposable elements (TEs) comprise nearly half of the human genome and play an essential role in the maintenance of genomic stability, chromosomal architecture, and transcriptional regulation. TEs are repetitive sequences consisting of RNA transposons, DNA transposons, and endogenous retroviruses that can invade the human genome with a substantial contribution in human evolution and genomic diversity. TEs are therefore firmly regulated from early embryonic development and during the entire course of human life by epigenetic mechanisms, in particular DNA methylation and histone modifications. The deregulation of TEs has been reported in some developmental diseases, as well as for different types of human cancers. To date, the role of TEs, the mechanisms underlying TE reactivation, and the interplay with DNA methylation in human cancers remain largely unexplained. We reviewed the loss of epigenetic regulation and subsequent genomic instability, chromosomal aberrations, transcriptional deregulation, oncogenic activation, and aberrations of non-coding RNAs as the potential mechanisms underlying TE deregulation in human cancers. PMID:28471386

Transposable Elements in Human Cancer: Causes and Consequences of Deregulation

Directory of Open Access Journals (Sweden)

Sumadi Lukman Anwar

2017-05-01

Full Text Available Transposable elements (TEs comprise nearly half of the human genome and play an essential role in the maintenance of genomic stability, chromosomal architecture, and transcriptional regulation. TEs are repetitive sequences consisting of RNA transposons, DNA transposons, and endogenous retroviruses that can invade the human genome with a substantial contribution in human evolution and genomic diversity. TEs are therefore firmly regulated from early embryonic development and during the entire course of human life by epigenetic mechanisms, in particular DNA methylation and histone modifications. The deregulation of TEs has been reported in some developmental diseases, as well as for different types of human cancers. To date, the role of TEs, the mechanisms underlying TE reactivation, and the interplay with DNA methylation in human cancers remain largely unexplained. We reviewed the loss of epigenetic regulation and subsequent genomic instability, chromosomal aberrations, transcriptional deregulation, oncogenic activation, and aberrations of non-coding RNAs as the potential mechanisms underlying TE deregulation in human cancers.

EFFECTS OF INTEREST RATE DEREGULATION ON AGRICULTURAL FINANCE AND GROWTH IN NIGERIA

Directory of Open Access Journals (Sweden)

Louis O. ONYISHI

2015-03-01

Full Text Available The study examined the effects of interest rate deregulation on agricultural finance and growth in Nigeria. The study specifically ascertained the factors that determine the aggregate credit volume to agriculture within the periods of regulation and deregulation in the Nigerian economy, determined the effects of government finance interventions on agricultural sector performance in the Nigerian economy, determined the periodic effects of macroeconomic financial indicators on Agriculture’s gross domestic product (GDP contribution to Nigerian economy and estimated the level of real credit growth of agricultural finance in Nigeria. Descriptive statistics, Ordinary Least Squares (OLS regression technique and chow test were used for data analysis. The chow test showed that there was a significant differential effect on the aggregate credit volume to agricultural sector between the regulated and deregulated regimes. Interest rate was an important determinant of aggregate credit volume to the agricultural sector in Nigeria, especially during the deregulated period but monetary authorities should ensure appropriate determination of interest rate level that will break the double-edge effect of interest rates on savers and investors.

Lowering electricity prices through deregulation

OpenAIRE

Thomas Klitgaard; Rekha Reddy

2000-01-01

A wave of regulatory reform is now transforming the U.S. electricity industry. As state and federal authorities allow independent power producers to compete with utilities in supplying electricity, consumers are paying close attention to the effects of this change on their energy bills. Although deregulation poses significant structural challenges, the introduction of competitive pressures should ultimately lead to efficiency gains for the industry and cost savings for households and businesses.

Structural Basis for Eculizumab-Mediated Inhibition of the Complement Terminal Pathway

DEFF Research Database (Denmark)

Schatz-Jakobsen, Janus Asbjørn; zhang, yuchun; Johnson, Krista

2016-01-01

the structural observations of the interaction are supported by the reduced ability of a subset of these mutated antibodies to inhibit MAC formation as tested in a hemolysis assay. Our results suggest that eculizumab functions by sterically preventing C5 from binding to convertases and explain the exquisite......Eculizumab is a humanized monoclonal antibody approved for treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uraemic syndrome. Eculizumab binds complement component C5 and prevents its cleavage by C5 convertases, inhibiting release of both...

Hepatic expression of the GH/JAK/STAT/IGF pathway, acute-phase response signalling and complement system are affected in mouse offspring by prenatal and early postnatal exposure to maternal high-protein diet.

Science.gov (United States)

Vanselow, Jens; Kucia, Marzena; Langhammer, Martina; Koczan, Dirk; Rehfeldt, Charlotte; Metges, Cornelia C

2011-12-01

Effects of pre- and early postnatal exposure to maternal high-protein diets are not well understood. Transcription profiling was performed in male mouse offspring exposed to maternal high-protein diet during pregnancy and/or lactation to identify affected hepatic molecular pathways. Dams were fed isoenergetic diets with control (20% w/w) or high protein levels (40%). The hepatic expression profiles were evaluated by differential microarray analysis 3 days (d3) and 3 weeks (d21) after birth. Offspring from three different high-protein dietary groups, HP (d3, high-protein diet during pregnancy), HPHP (d21, high-protein diet during pregnancy and lactation) and CHP (d21, control diet during pregnancy and high-protein diet during lactation), were compared with age-matched offspring from dams fed control diet. Offspring body and liver mass of all high-protein groups were decreased. Prenatal high-protein diet affected hepatic expression of genes mapping to the acute response/complement system and the GH/JAK/STAT/IGF signalling pathways. Maternal exposure to high-protein diet during lactation affected hepatic gene expression of the same pathways but additionally affected genes mapping to protein, fatty acid, hexose and pyruvate metabolism. (1) Genes of the acute response/complement system and GH/JAK/STAT/IGF pathways were down-regulated in offspring of dams exposed to high-protein diets during pregnancy and/or lactation. (2) Genes related to nutrient and energy metabolism, however, were only affected when high-protein diet was administered during lactation. (3) Modulation of the GH/JAK/STAT/IGF pathway might be responsible for reduced body and liver masses by maternal high-protein diet.

X-ray repair cross complementing protein 1 in base excision repair

DEFF Research Database (Denmark)

Hanssen-Bauer, Audun; Solvang-Garten, Karin; Akbari, Mansour

2012-01-01

X-ray Repair Cross Complementing protein 1 (XRCC1) acts as a scaffolding protein in the converging base excision repair (BER) and single strand break repair (SSBR) pathways. XRCC1 also interacts with itself and rapidly accumulates at sites of DNA damage. XRCC1 can thus mediate the assembly of large...

Customer choice: Purchasing energy in a deregulated market

International Nuclear Information System (INIS)

Thumann, A.

1999-01-01

This book presents the detailed guidance on how to effectively purchase deregulated energy, based on first-hand reports from many of the nation's most knowledgeable experts. It is designed to provide the kind of practical advice needed by professionals who are responsible for making energy purchasing decisions. The book gives a ten-step program to guide building owners in purchasing decision making, a state-by-state retail competition update, and guidelines for buying electricity and natural gas over the worldwide web. Other topics include contract renegotiation strategies, an assessment of power pools, the role of aggregators in the energy market, real time pricing issues, where cogeneration fits within today's marketplace, and lessons learned from deregulation experiences in Scandinavia and England

Current issues in Canadian electricity deregulation and competition

Energy Technology Data Exchange (ETDEWEB)

Roman, A.J. [Calgary Univ., Calgary, AB (Canada). Canadian Inst. of Resources Law

1998-03-30

The deregulation of the electricity industry in Canada was the main focus of this paper. In most developed countries, industries formerly dominated by a monopoly service provider have already been significantly restructured through the introduction of competition. In Canada, such restructuring has taken place only in the airline, railway, natural gas and telephone industry. In most Canadian provinces, except Alberta, electricity generation, transmission and distribution is still owned and operated by provincial and municipal governments. This report examines the present situation in electricity deregulation in Alberta, provides a summary of analysis of London Economics Inc.`s proposals and Bill 27, and presents the author`s own conclusions. A broader perspective and context is provided by references to other regulations of other industries throughout the report.

The German Political Economy Between Deregulation and Re-regulation: Party Discourses on Minimum Wage Policies

OpenAIRE

Dostal, Jörg Michael

2012-01-01

In the German political economy of the early 21st century, labor market policymaking has shifted toward deregulation and liberalization. In particular, the so-called Hartz labor market reforms of the Social Democratic Party and Green Party government, introduced in 2002 and 2003, pushed for employment growth in low-wage and deregulated employment sectors. This article focuses on one of the key debates triggered by Germany’s labor market deregulation after 2002, namely whethe...

Generation capacity expansion planning in deregulated electricity markets

Science.gov (United States)

Sharma, Deepak

With increasing demand of electric power in the context of deregulated electricity markets, a good strategic planning for the growth of the power system is critical for our tomorrow. There is a need to build new resources in the form of generation plants and transmission lines while considering the effects of these new resources on power system operations, market economics and the long-term dynamics of the economy. In deregulation, the exercise of generation planning has undergone a paradigm shift. The first stage of generation planning is now undertaken by the individual investors. These investors see investments in generation capacity as an increasing business opportunity because of the increasing market prices. Therefore, the main objective of such a planning exercise, carried out by individual investors, is typically that of long-term profit maximization. This thesis presents some modeling frameworks for generation capacity expansion planning applicable to independent investor firms in the context of power industry deregulation. These modeling frameworks include various technical and financing issues within the process of power system planning. The proposed modeling frameworks consider the long-term decision making process of investor firms, the discrete nature of generation capacity addition and incorporates transmission network modeling. Studies have been carried out to examine the impact of the optimal investment plans on transmission network loadings in the long-run by integrating the generation capacity expansion planning framework within a modified IEEE 30-bus transmission system network. The work assesses the importance of arriving at an optimal IRR at which the firm's profit maximization objective attains an extremum value. The mathematical model is further improved to incorporate binary variables while considering discrete unit sizes, and subsequently to include the detailed transmission network representation. The proposed models are novel in the

Cell cycle deregulation by the HBx protein of hepatitis B virus

Directory of Open Access Journals (Sweden)

Vijay Kumar

2007-02-01

Full Text Available

Cell cycle control by oncogenic viruses usually involves disruption of the normal restraints on cellular proliferation via abnormal proteolytic degradation and malignant transformation of cells. The cell cycle regulatory molecules viz. cyclins, cyclin-dependent kinases (cdks and inhibitors of cdks as well as the transcriptional targets of signaling pathways induce cells to move through the cell cycle checkpoints. These check points are often found deregulated in tumor cells and in the cells afflicted with DNA tumor viruses predisposing them towards transformation. The X protein or HBx of hepatitis B virus is a promiscuous transactivator that has been implicated in the development of hepatocellular carcinoma in humans. However, the exact role of HBx in establishing a permissive environment for hepatocarcinogenesis is not fully understood. HBx activates the Ras-Raf-MAP kinase signaling cascade, through which it activates transcription factors AP-1 and NFkappa B, and stimulates cell DNA synthesis. HBx shows a profound effect on cell cycle progression even in the absence of serum. It can override the replicative senescence of cells in G0 phase by binding to p55sen. It stimulates the G0 cells to transit through G1 phase by activating Src kinases and the cyclin A-cyclin-dependent kinase 2 complexes, that in turn induces the cyclin A promoter. There is an early and sustained level of cyclin-cdk2 complex in the presence of HBx during the cell cycle which is coupled with an increased protein kinase activity of cdk2 suggesting an early appearance of S phase. The interaction between cyclin-cdk2 complex and HBx occurs through its carboxyterminal region (amino acids 85-119 and requires a constitutive Src kinase activity. The increased cdk2 activity is associated with stabilization of cyclin E as well as proteasomal degradation of cdk inhibitor p27Kip1. Notably, the HBx mutant

Tumour exosomes display different differential mechanical and complement activation properties dependent on malignant state: implications in endothelial leakiness

DEFF Research Database (Denmark)

Whitehead, Bradley Joseph; Wu, Linping; Hvam, Michael Lykke

2015-01-01

(QNM AFM) to determine size and nanomechanical properties. Effect of HCV-29, T24 and FL3 exosomes on human umbilical vein endothelial cell (HUVEC) monolayer integrity was determined by transendothelial electrical resistance (TEER) measurements and transport was determined by flow cytometry. Complement......). Malignant cell-derived exosomes activated complement through calcium-sensitive pathways in a concentration-dependent manner. Conclusions : Malignant (metastatic and non-metastatic) cell line exosomes display a markedly reduced stiffness and adhesion but an increased complement activation compared to non...

75 FR 68321 - Forage Genetics International; Supplemental Request for Partial Deregulation of Roundup Ready...

Science.gov (United States)

2010-11-05

...] Forage Genetics International; Supplemental Request for Partial Deregulation of Roundup Ready Alfalfa... Inspection Service has received a supplemental request for ``partial deregulation'' from Forage Genetics... affected persons of the availability of the documents submitted to the Agency from Forage Genetics...

Complement factor H family proteins in their non-canonical role as modulators of cellular functions.

Science.gov (United States)

Józsi, Mihály; Schneider, Andrea E; Kárpáti, Éva; Sándor, Noémi

2018-01-04

Complement factor H is a major regulator of the alternative pathway of the complement system. The factor H-related proteins are less characterized, but recent data indicate that they rather promote complement activation. These proteins have some common ligands with factor H and have both overlapping and distinct functions depending on domain composition and the degree of conservation of amino acid sequence. Factor H and some of the factor H-related proteins also appear in a non-canonical function that is beyond their role in the modulation of complement activation. This review covers our current understanding on this emerging role of factor H family proteins in modulating the activation and function of various cells by binding to receptors or receptor ligands. Copyright © 2018 Elsevier Ltd. All rights reserved.

Competitive nuclear production on the nordic deregulated electricity market

International Nuclear Information System (INIS)

Bohl, T.

2000-01-01

The Nordic electricity market has been partly deregulated since 1994. Today only Denmark follows the timetable recommended by the European Union, while Sweden, Norway and Finland are completely deregulated. As in most countries, the production of electricity is deregulated while the distribution is still a monopoly. This deregulation of the electricity market has created a new situation for plant life management. In order to be competitive on the market it is important to cut cost down a level when the nuclear power companies earn money again. All means to cut cost have to be used while still maintaining safety and the possibilities for operation over at least 40+ years. The possibilities to invest in modernization are limited to the absolutely necessary modifications. All investments must be very thoroughly questioned and the money can only be spent where most benefit is gained. This means new prerequisites for the absolute necessary long-strategic planning. New safety requirements from the authorities have to be discussed between the industry and the authority. The requirement cost must be compared to the benefit to safety. The authority is today requested to carry out such analyses and do so in most cases. Since the electricity market is international the requirements of the authorities must be harmonized on the whole market. The political threat against nuclear power is serious in many countries and it is important to continue working with public acceptance and lobbying. Especially in Sweden a lot of effort is spent on trying to change the taxation of nuclear power. In the near future increasing electricity demand will make the prices go up to a level when nuclear power companies earn money again. The very serious worries about climate change will also strengthen the competitiveness of nuclear power. (author)

A tick mannose-binding lectin inhibitor interferes with the vertebrate complement cascade to enhance transmission of the lyme disease agent.

Science.gov (United States)

Schuijt, Tim J; Coumou, Jeroen; Narasimhan, Sukanya; Dai, Jianfeng; Deponte, Kathleen; Wouters, Diana; Brouwer, Mieke; Oei, Anneke; Roelofs, Joris J T H; van Dam, Alje P; van der Poll, Tom; Van't Veer, Cornelis; Hovius, Joppe W; Fikrig, Erol

2011-08-18

The Lyme disease agent Borrelia burgdorferi is primarily transmitted to vertebrates by Ixodes ticks. The classical and alternative complement pathways are important in Borrelia eradication by the vertebrate host. We recently identified a tick salivary protein, designated P8, which reduced complement-mediated killing of Borrelia. We now discover that P8 interferes with the human lectin complement cascade, resulting in impaired neutrophil phagocytosis and chemotaxis and diminished Borrelia lysis. Therefore, P8 was renamed the tick salivary lectin pathway inhibitor (TSLPI). TSLPI-silenced ticks, or ticks exposed to TSLPI-immune mice, were hampered in Borrelia transmission. Moreover, Borrelia acquisition and persistence in tick midguts was impaired in ticks feeding on TSLPI-immunized, B. burgdorferi-infected mice. Together, our findings suggest an essential role for the lectin complement cascade in Borrelia eradication and demonstrate how a vector-borne pathogen co-opts a vector protein to facilitate early mammalian infection and vector colonization. Copyright © 2011 Elsevier Inc. All rights reserved.

Coordinated Expression of Borrelia burgdorferi Complement Regulator-Acquiring Surface Proteins during the Lyme Disease Spirochete's Mammal-Tick Infection Cycle▿

OpenAIRE

Bykowski, Tomasz; Woodman, Michael E.; Cooley, Anne E.; Brissette, Catherine A.; Brade, Volker; Wallich, Reinhard; Kraiczy, Peter; Stevenson, Brian

2007-01-01

The Lyme disease spirochete, Borrelia burgdorferi, is largely resistant to being killed by its hosts’ alternative complement activation pathway. One possible resistance mechanism of these bacteria is to coat their surfaces with host complement regulators, such as factor H. Five different B. burgdorferi outer surface proteins having affinities for factor H have been identified: complement regulator-acquiring surface protein 1 (BbCRASP-1), encoded by cspA; BbCRASP-2, encoded by cspZ; and three ...

Inflow shortages in deregulated power markets - Reasons for concern?

International Nuclear Information System (INIS)

Bye, Torstein; Bruvoll, Annegrete; Aune, Finn Roar

2008-01-01

In many countries hydropower constitutes a large share of the electricity producing capacity. In the earlier regulated electricity markets, production capacities exceeded demand due to security of supply concerns. The present deregulated markets base investments upon profitability alone, and security of supply issues are claimed to be less important. Market operators trust the pricing mechanism in competitive markets to clear. Then low inflow constitutes a less problem. Several markets, both under regulated and deregulated regimes, have faced serious droughts. Some of them have experienced problems with market clearance (Chile, Brazil, California) while other markets functioned well (The Nordic market). Important features to the market response are the flexibility of demand, the pattern of inflow shortage, the storage capacities, the possibility of trade between regions with different production technologies, and the market design and concentration. We apply an empirical based market model to simulate the effects under two inflow shortage scenarios in an international market with combined hydro and thermal capacities and restricted transmission capacities. We compare the scenarios with actual events and show that the model and the real market outcome are comparable. The simulations do not reveal any problems with the functioning of the market, which should calm down the anxiousness about security of supply in deregulated markets with stochastic energy supply

Inflow shortages in deregulated power markets - Reasons for concern?

Energy Technology Data Exchange (ETDEWEB)

Bye, Torstein; Bruvoll, Annegrete; Aune, Finn Roar [Research Department, Statistics Norway, P.O. Box 8131 Dep., 0033 Oslo (Norway)

2008-07-15

In many countries hydropower constitutes a large share of the electricity producing capacity. In the earlier regulated electricity markets, production capacities exceeded demand due to security of supply concerns. The present deregulated markets base investments upon profitability alone, and security of supply issues are claimed to be less important. Market operators trust the pricing mechanism in competitive markets to clear. Then low inflow constitutes a less problem. Several markets, both under regulated and deregulated regimes, have faced serious droughts. Some of them have experienced problems with market clearance (Chile, Brazil, California) while other markets functioned well (The Nordic market). Important features to the market response are the flexibility of demand, the pattern of inflow shortage, the storage capacities, the possibility of trade between regions with different production technologies, and the market design and concentration. We apply an empirical based market model to simulate the effects under two inflow shortage scenarios in an international market with combined hydro and thermal capacities and restricted transmission capacities. We compare the scenarios with actual events and show that the model and the real market outcome are comparable. The simulations do not reveal any problems with the functioning of the market, which should calm down the anxiousness about security of supply in deregulated markets with stochastic energy supply. (author)

Deregulation : unlocking value : the Australian experience

International Nuclear Information System (INIS)

Kwok, F.

2002-01-01

Macquarie is a global investment bank based in Australia whose international focus is on niche markets such as infrastructure and utilities. A corporate review of Macquarie is presented along with a review of the evolution of the utility industry from the stages of an integrated utility to fully unbundled entities. In the first stage, the utility is vertically integrated and owned by government, or it is highly regulated. The second stage of evolution involves the unbundling of the utility into separate generation, transmission and distribution companies, each preparing for competition. The third stage involves the introduction of competition to power generation and retail sectors. Transmission and distribution remains regulated in the third stage. The fourth stage involves down-sizing in response to competition and benchmarking. It is also a period of convergence between electricity and gas. The fifth and final stage is for deriving value. Deregulation results in major structural changes and utility managers have to decide how the utility can best deliver value to the shareholders in the new environment. The author discusses how these lessons can be applied to the case of electric power industry deregulation in Alberta

Effect of truck and rail economic deregulation on radioactive material transportation

International Nuclear Information System (INIS)

Allen, G.C. Jr.

1984-01-01

An evaluation of the effect of truck and rail economic deregulation on radioactive material transportation is presented in this document. The evaluation is based on expected market performance that would be consistent with fundamental economic theories. The issues of transport safety, commodity discrimination and rates are addressed. Relative to transport safety, deregulation should not have any significant impact. While deregulation should not change commodity acceptance and may lower rates for motor carriage, it may allow increased discrimination by rail carriers in addition to raising rates. Consequently, it is likely that the radioactive material transportation industry will continue to place greater reliance on the competitive motor carrier industry. Positive steps that shippers can take are to maintain credible options to ship by alternate modes, to address issues that result in the perceived need for special risk premiums, and to reduce the cost of handling truck shipments by improvements in technology or procedures. 28 references, 3 figures, 6 tables

Pricing behaviour of pharmacies after market deregulation for OTC drugs: the case of Germany.

Science.gov (United States)

Stargardt, Tom; Schreyögg, Jonas; Busse, Reinhard

2007-11-01

To examine the price reactions of German pharmacies to changes made to OTC drug regulations in 2004. Prior to these changes, regulations guaranteed identical prices in all German pharmacies. Two years after market deregulation, 256 pharmacies were surveyed to determine the retail prices of five selected OTC drugs. A probit regression model was used to identify factors that increased the likelihood of price changes. In addition, 409 pharmacy consumers were interviewed to gather information on their knowledge of the regulatory changes and to better explain consumer behaviour. Data was collected on a total of 1215 prices. Two years after deregulation, 23.1% of the participating pharmacies had modified the price of at least one of the five OTCs included in our study. However, in total, only 7.5% of the prices differed from their pre-deregulation level. The probit model showed that population density and the geographic concentration of pharmacies were significantly associated with price changes. Interestingly, the association with the geographic concentration of pharmacies was negative. The consumer survey revealed that 47.1% of those interviewed were aware of the deregulation. Our findings indicate that, two years after deregulation, very few pharmacies had made use of individual pricing strategies; price competition between pharmacies in Germany is thus taking place only a very small scale.

Deregulation of Lesotho's maize market

OpenAIRE

van Schalkwyk, Herman D.; van Zyl, Johan; Botha, P.W.; Bayley, B.

1997-01-01

During the past year, there have been major policy reforms in Lesotho and South Africa with respect to maize pricing and marketing. In Lesotho the impact of deregulation on producers, consumers and government revenues was substantially lower than it should have been, and as a result Lesotho was not able to reap the full benefits of these changes. This is partly because information on the changes to the maize marketing system did not reach the potential beneficiaries of the new system. Free an...

From public good to private exploitation : electricity deregulation, privatization and continental integration

International Nuclear Information System (INIS)

Griffin Cohen, M.

2002-07-01

A study was conducted to examine the initiative of the World Trade Organization (WTO) on energy taking place through negotiations on the General Agreement on Trade in Services (GATS), which coincide with the U.S. drive for integrated continental energy policy. These negotiations will affect the nature of the electricity industry in Canada. It was noted that if the U.S. proposal for energy in GATS succeeds, it would support complete electricity deregulation, privatization of power generation, and full-scale continental pricing. This report includes several chapters. The chapter on electricity deregulation deals with changes in the electricity industry and the U.S. drive for energy. The GATS chapter describes the main features of GATS and what it covers, including general obligations, disciplines and negotiations. The chapter on the electricity industry in Canada describes major features, major electrical utilities, exports and the state of deregulation in Canada's 10 provinces. The chapter on GATS implications for electrical utilities focused on deregulation and market power, the implications for developing nations and general environmental issues. It was cautioned that if a Canadian agreement were to include electricity as a covered industry, it could erode the security of supply, drive prices up and have negative consequences for energy conservation. 137 refs., 8 tabs

Why electricity deregulation is likely to fail: An explanation with an application to Israel

Energy Technology Data Exchange (ETDEWEB)

Tishler, Asher; Woo, Chi-Keung

2005-12-15

In this paper we contend that electricity deregulation likely fails because of a fundamental, but so far ignored, reason. In particular, a deregulated electricity market cannot have too many producers because they will not be able to recover their investment costs. Nor can it have too few producers because the resulting market price will likely exceed the regulated rate. If constrained by the financial viability of privately owned generators and an overarching goal of unregulated market price not exceeding the regulated rate, the set of feasible numbers of producers in the competitive market can be very small, and at times empty. Our theoretical prediction applies to deregulation of other industries with large fixed and sunk costs (e.g., gas transportation, electricity transmission and distribution, local telecom networks, ports, railways, etc.). We show that a large improvement in the operational efficiency of the deregulated industry is a necessary condition for a successful deregulation of the industry. Unfortunately, operation improvement in electricity generation is limited because fuel (e.g., coal, oil, natural gas, and liquefied natural gas) and generation equipment (e.g., turbines, transformers, and cables), which constitute about 80% of the total cost of electricity generation, are commodities traded in a competitive world market. Thus, cost savings due to deregulation in the electricity generation market mainly come from efficiency improvement in capacity investment and variable input use of labor and O and M. Unless the regulated integrated utility has been investing inefficiently in surplus capacity, such savings, mainly in labor and O and M, are unlikely to produce more than a 10% reduction in total generation cost. For this reason and based on the experience to date, we caution against deregulation in regions that currently have a regulated electricity sector (e.g., China, India, Hong Kong, Israel, Africa, and many parts of North America). Our

Why electricity deregulation is likely to fail: An explanation with an application to Israel

International Nuclear Information System (INIS)

Tishler, Asher; Woo, Chi-Keung

2005-01-01

In this paper we contend that electricity deregulation likely fails because of a fundamental, but so far ignored, reason. In particular, a deregulated electricity market cannot have too many producers because they will not be able to recover their investment costs. Nor can it have too few producers because the resulting market price will likely exceed the regulated rate. If constrained by the financial viability of privately owned generators and an overarching goal of unregulated market price not exceeding the regulated rate, the set of feasible numbers of producers in the competitive market can be very small, and at times empty. Our theoretical prediction applies to deregulation of other industries with large fixed and sunk costs (e.g., gas transportation, electricity transmission and distribution, local telecom networks, ports, railways, etc.). We show that a large improvement in the operational efficiency of the deregulated industry is a necessary condition for a successful deregulation of the industry. Unfortunately, operation improvement in electricity generation is limited because fuel (e.g., coal, oil, natural gas, and liquefied natural gas) and generation equipment (e.g., turbines, transformers, and cables), which constitute about 80% of the total cost of electricity generation, are commodities traded in a competitive world market. Thus, cost savings due to deregulation in the electricity generation market mainly come from efficiency improvement in capacity investment and variable input use of labor and O and M. Unless the regulated integrated utility has been investing inefficiently in surplus capacity, such savings, mainly in labor and O and M, are unlikely to produce more than a 10% reduction in total generation cost. For this reason and based on the experience to date, we caution against deregulation in regions that currently have a regulated electricity sector (e.g., China, India, Hong Kong, Israel, Africa, and many parts of North America). Our

Aneuploidy-Dependent Massive Deregulation of the Cellular Transcriptome and Apparent Divergence of the Wnt/β-catenin Signaling Pathway in Human Rectal Carcinomas

Science.gov (United States)

Grade, Marian; Ghadimi, B. Michael; Varma, Sudhir; Simon, Richard; Wangsa, Danny; Barenboim-Stapleton, Linda; Liersch, Torsten; Becker, Heinz; Ried, Thomas; Difilippantonio, Michael J.

2016-01-01

To identify genetic alterations underlying rectal carcinogenesis, we used global gene expression profiling of a series of 17 locally advanced rectal adenocarcinomas and 20 normal rectal mucosa biopsies on oligonucleotide arrays. A total of 351 genes were differentially expressed (P 5-fold difference, and 85 genes always had at least a 2-fold change in all of the matched samples. Twelve genes satisfied all three of these criteria. Altered expression of genes such as PTGS2 (COX-2), WNT1, TGFB1, VEGF, and MYC was confirmed, whereas our data for other genes, like PPARD and LEF1, were inconsistent with previous reports. In addition, we found deregulated expression of many genes whose involvement in rectal carcinogenesis has not been reported. By mapping the genomic imbalances in the tumors using comparative genomic hybridization, we could show that DNA copy number gains of recurrently aneuploid chromosome arms 7p, 8q, 13q, 18q, 20p, and 20q correlated significantly with their average chromosome arm expression profile. Taken together, our results show that both the high-level, significant transcriptional deregulation of specific genes and general modification of the average transcriptional activity of genes residing on aneuploid chromosomes coexist in rectal adenocarcinomas. PMID:16397240

Vulnerable Consumers in the Deregulated Dutch Health System

NARCIS (Netherlands)

Booltink, L.; Genugten, M.L. van; Lako, C.J.

2015-01-01

Public service deregulation is favoured for motivating providers to offer consumers better price-quality services. Consequently, consumers are enabled to make informed choices and choose for the best service provider. However, recent publications reveal that consumers are not capable of exercising

A study on the deregulation of the Finnish electricity markets

International Nuclear Information System (INIS)

Kopsakangas-Savolainen, M.

2002-01-01

Governments have regarded the electricity industry as a leading industrial sector throughout the history. Because of its strategic importance to industrial development, its impacts on the social and environmental issues and its natural monopoly characteristics, it has been seen necessary to regulate electricity industry effectively. However, in the mid 1980s it was realised that even though transmission and distribution networks are natural monopolies, the scale economies in electricity production at the generating unit level had exhausted at a unit size of about 500 MW. This meant that supply and generation had become potentially competitive activities. In Finland the new Electricity Market Act (EMA) came into force in 1.11.1995. According to it the production and supply of electricity became deregulated and competition was introduced to the industry. The main aim of the law was to improve efficiency. This dissertation analyses, both theoretically and empirically, the impacts of deregulation to the Finnish electricity markets. In chapter two we discuss on the grounds and incentives of the deregulation processes that have been carried out in different countries. We also determine the crucial factors in order succeed in the deregulation process. According to our view the success depend on the number of active players in the wholesale market, the rules of the bidding procedure, the organisation of the demand side operation, the neutrality of transmission grid, the structure of production technologies and the ownership structure of the industry. In chapter three we theoretically model the profit maximising behaviour of the Finnish electricity companies based on different stages of vertical integration and on different stage of competition. According to our results the profit maximising pricing rules of distribution units is dependent on the stage of integration and on the stage of competition. The separated distribution company maximises profits by setting the

Developmentally regulated expression by Trypanosoma cruzi of molecules that accelerate the decay of complement C3 convertases

International Nuclear Information System (INIS)

Rimoldi, M.T.; Sher, A.; Heiny, A.; Lituchy, A.; Hammer, C.H.; Joiner, K.

1988-01-01

The authors recently showed that culture-derived metacyclic trypomastigotes (CMT), but not epimastigotes (Epi), of the Miranda 99 strain of Trypanosoma cruzi evade lysis by the human alternative complement pathway because of inefficient binding of factor B to complement component C3b on the parasite surface. These results suggested that CMT and tissue-culture-derived trypomastigotes (TCT), which also activate the alternative pathway poorly, might produce a molecule capable of interfering with factor B binding to C3b. They now demonstrate that CMT and TCT lysates, as well as molecules spontaneously shed from CMT and TCT but not Epi, accelerate decay of 125 I-labeled factor Bb from the alternative-pathway C3 convertase (C3bBb) assembled on zymosan or Epi and also accelerate decay of the classical-pathway C3 convertase (C4b2a) on sheep erythrocytes. Parasites metabolically labeled with [ 35 S]methionine spontaneously shed a limited number of radioactive components, ranging in molecular mass from 86 to 155 kDa for trypomastigotes and 25 to 80 kDa for Epi. Decay-accelerating activity within supernatants is inactivated by papain and is coeluted with 35 S-containing polypeptides on FPLC anion-exchange chromatography, suggesting that the active constituents are protein molecules. Molecules with decay-accelerating activity may explain the developmentally regulated resistance to complement-mediated lysis in infective and vertebrate stages for T. cruzi life cycle

A Metalloproteinase Mirolysin of Tannerella forsythia Inhibits All Pathways of the Complement System

DEFF Research Database (Denmark)

Jusko, Monika; Potempa, Jan; Mizgalska, Danuta

2015-01-01

Recent reports focusing on virulence factors of periodontal pathogens implicated proteinases as major determinants of remarkable pathogenicity of these species, with special emphasis on their capacity to modulate complement activity. In particular, bacteria-mediated cleavage of C5 and subsequent...... release of C5a seems to be an important phenomenon in the manipulation of the local inflammatory response in periodontitis. In this study, we present mirolysin, a novel metalloproteinase secreted by Tannerella forsythia, a well-recognized pathogen strongly associated with periodontitis. Mirolysin...... with karilysin, as well as a cysteine proteinase of another periodontal pathogen, Prevotella intermedia, resulted in a strong synergistic effect on complement. Furthermore, mutant strains of T. forsythia, devoid of either mirolysin or karilysin, showed diminished survival in human serum, providing further...

Omics-Based Approach Reveals Complement-Mediated Inflammation in Chronic Lymphocytic Inflammation With Pontine Perivascular Enhancement Responsive to Steroids (CLIPPERS

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Morten Blaabjerg

2018-04-01

Full Text Available ObjectiveChronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS is a rare syndrome with relapsing brainstem/cerebellar symptoms. To examine the pathogenic processes and investigate potential biomarkers, we analyzed combined materials of brain and cerebrospinal fluid (CSF by comprehensive methodologies.Materials and methodsTo identify major pathways of perivascular inflammation in CLIPPERS, we first compared the CSF proteome (n = 5 to a neurodegenerative condition, Alzheimer’s disease (AD, n = 5. Activation of complement was confirmed by immunohistochemistry (IHC on CLIPPERS brain samples (n = 3 and by ELISA in the CSF. For potential biomarkers, we used biomarker arrays, and compared inflammatory and vessel-associated proteins in the CSF of CLIPPERS (n = 5 with another inflammatory relapsing CNS disease, multiple sclerosis (RMS, n = 9 and healthy subjects (HS, n = 7.ResultsTwo hundred and seven proteins in the CSF discriminated CLIPPERS from AD. The complement cascade, immunoglobulins, and matrix proteins were among the most frequently represented pathways. Pathway analysis of upstream regulators suggested the importance of vascular cell adhesion protein 1 (VCAM1, IFN-γ, interleukin (IL-1, and IL-10. Differential regulation of more than 10 complement proteins of the 3 complement pathways in the CSF pointed to the role of complement activation. IHC on brain samples confirmed the perivascular complement activation, i.e., deposition of C3bc, C3d, and the terminal C5b-9 complement complex that partially overlapped with accumulation of IgG in the vessel wall. Besides endothelial cell damage, reactivity to smooth muscle actin was lost in the walls of inflamed vessels, but the glia limitans was preserved. The semi-quantitative array indicated that increased level of IL-8/CXCL8 (p < 0.05, eotaxin/CCL11 (p < 0.01, and granulocyte colony-stimulating factor (p < 0.05 in

Genome Mining of the Marine Actinomycete Streptomyces sp. DUT11 and Discovery of Tunicamycins as Anti-complement Agents

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Xiao-Na Xu

2018-06-01

Full Text Available Marine actinobacteria are potential producers of various secondary metabolites with diverse bioactivities. Among various bioactive compounds, anti-complement agents have received great interest for drug discovery to treat numerous diseases caused by inappropriate activation of the human complement system. However, marine streptomycetes producing anti-complement agents are still poorly explored. In this study, a marine-derived strain Streptomyces sp. DUT11 showing superior anti-complement activity was focused, and its genome sequence was analyzed. Gene clusters showing high similarities to that of tunicamycin and nonactin were identified, and their corresponding metabolites were also detected. Subsequently, tunicamycin I, V, and VII were isolated from Streptomyces sp. DUT11. Anti-complement assay showed that tunicamycin I, V, VII inhibited complement activation through the classic pathway, whereas no anti-complement activity of nonactin was detected. This is the first time that tunicamycins are reported to have such activity. In addition, genome analysis indicates that Streptomyces sp. DUT11 has the potential to produce novel lassopeptides and lantibiotics. These results suggest that marine Streptomyces are rich sources of anti-complement agents for drug discovery.

Improving firm performance in out-of-equilibrium, deregulated markets using feedback simulation models

International Nuclear Information System (INIS)

Gary, S.; Larsen, E.R.

2000-01-01

Deregulation has reshaped the utility sector in many countries around the world. Organisations in these deregulated industries must adopt new polices which guide strategic decisions, in an uncertain and unfamiliar environment, that determine the short- and long-term fate of their companies. Traditional economic equilibrium models do not adequately address the issues facing these organisations in the shift towards deregulated market competition. Equilibrium assumptions break down in the out-of-equilibrium transition to competitive markets, and therefore different underpinning assumptions must be adopted in order to guide management in these periods. Simulation models incorporating information feedback through behavioural policies fill the void left by equilibrium models and support strategic policy analysis in out-of-equilibrium markets. As an example, we present a feedback simulation model developed to examine firm and industry level performance consequences of new generation capacity investment policies in the deregulated UK electricity sector. The model explicitly captures behavioural decision polices of boundedly rational managers and avoids equilibrium assumptions. Such models are essential to help managers evaluate the performance impact of various strategic policies in environments in which disequilibrum behaviour dominates. (Author)

Energy service unbundling: where deregulation is heading

International Nuclear Information System (INIS)

Croft, M.

2002-01-01

The workings of the natural gas market is provided by the speaker at the beginning of the presentation, and covers pre-regulation, early regulation and deregulation. The pre-regulation era provided no customer choice, and the early regulation period saw industrial customers with some degree of choice (mid-1980s). The advent of deregulation created core market customer choice (around 1996). At Coral Energy, there is choice of energy supplier, choice of price structure, and choice of transportation and distribution. A forecast of North American gas demand is provided, along with the natural gas supply and the North American gas supply basins. For the period January 1996 to May 2000, a comparison of annualized volatility is discussed. The author discusses the strategies for purchasing gas: 1) to know yourself and your risk tolerance, flexibility, and load profile; 2) switching gas supply provider. It is important to choose a three year term, combination pricing, and storage position. The risk management options are reviewed: limit exposure to price volatility, mitigate price/volume volatility, and enhance bottom line by capturing market opportunities. figs

Analysis of Deregulated microRNAs and Their Target Genes in Gastric Cancer.

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Simonas Juzėnas

Full Text Available MicroRNAs (miRNAs are widely studied non-coding RNAs that modulate gene expression. MiRNAs are deregulated in different tumors including gastric cancer (GC and have potential diagnostic and prognostic implications. The aim of our study was to determine miRNA profile in GC tissues, followed by evaluation of deregulated miRNAs in plasma of GC patients. Using available databases and bioinformatics methods we also aimed to evaluate potential target genes of confirmed differentially expressed miRNA and validate these findings in GC tissues.The study included 51 GC patients and 51 controls. Initially, we screened miRNA expression profile in 13 tissue samples of GC and 12 normal gastric tissues with TaqMan low density array (TLDA. In the second stage, differentially expressed miRNAs were validated in a replication cohort using qRT-PCR in tissue and plasma samples. Subsequently, we analyzed potential target genes of deregulated miRNAs using bioinformatics approach, determined their expression in GC tissues and performed correlation analysis with targeting miRNAs.Profiling with TLDA revealed 15 deregulated miRNAs in GC tissues compared to normal gastric mucosa. Replication analysis confirmed that miR-148a-3p, miR-204-5p, miR-223-3p and miR-375 were consistently deregulated in GC tissues. Analysis of GC patients' plasma samples showed significant down-regulation of miR-148a-3p, miR-375 and up-regulation of miR-223-3p compared to healthy subjects. Further, using bioinformatic tools we identified targets of replicated miRNAs and performed disease-associated gene enrichment analysis. Ultimately, we evaluated potential target gene BCL2 and DNMT3B expression by qRT-PCR in GC tissue, which correlated with targeting miRNA expression.Our study revealed miRNA profile in GC tissues and showed that miR-148a-3p, miR-223-3p and miR-375 are deregulated in GC plasma samples, but these circulating miRNAs showed relatively weak diagnostic performance as sole biomarkers

The regulation and deregulation of Wnt signaling by PARK genes in health and disease.

Science.gov (United States)

Berwick, Daniel C; Harvey, Kirsten

2014-02-01

Wingless/Int (Wnt) signaling pathways are signal transduction mechanisms that have been widely studied in the field of embryogenesis. Recent work has established a critical role for these pathways in brain development, especially of midbrain dopaminergic neurones. However, the fundamental importance of Wnt signaling for the normal function of mature neurones in the adult central nervous system has also lately been demonstrated by an increasing number of studies. Parkinson's disease (PD) is the second most prevalent neurodegenerative disease worldwide and is currently incurable. This debilitating disease is characterized by the progressive loss of a subset of midbrain dopaminergic neurones in the substantia nigra leading to typical extrapyramidal motor symptoms. The aetiology of PD is poorly understood but work performed over the last two decades has identified a growing number of genetic defects that underlie this condition. Here we review a growing body of data connecting genes implicated in PD--most notably the PARK genes--with Wnt signaling. These observations provide clues to the normal function of these proteins in healthy neurones and suggest that deregulated Wnt signaling might be a frequent pathomechanism leading to PD. These observations have implications for the pathogenesis and treatment of neurodegenerative diseases in general.

Investigation of radiation-induced multilayered signalling response of the inflammatory pathway

International Nuclear Information System (INIS)

Babini, G.; Ugolini, M.; Morini, J.; Baiocco, G.; Ottolenghi, A.; Mariotti, L.; Tabarelli de Fatis, P.; Liotta, M.

2015-01-01

Ionising radiation exposure of cells might induce the perturbation of cell functions and, in particular, the activation or inhibition of several important pathways. This perturbation can cause the deregulation of both intra- and extra-cellular signalling cascades (such as the inflammatory pathway) and alter not only the behaviour of directly exposed cells but also the neighbouring nonirradiated ones, through the so-called bystander effect. The aim of the present work was to investigate the complex nonlinear interactions between the inflammatory pathway and other strictly interlaced signalling pathways, such as Erk1/2 and Akt/PKB, focusing on the radiation-induced perturbation of such pathways in the dose range of 0 -2 Gy. The results show how radiation affects these interconnected pathways and how confounding factors, such as the change of culture medium, can hide radiation-induced perturbations. (authors)

Shark complement: an assessment.

Science.gov (United States)

Smith, S L

1998-12-01

The classical (CCP) and alternative (ACP) pathways of complement activation have been established for the nurse shark (Ginglymostoma cirratum). The isolation of a cDNA clone encoding a mannan-binding protein-associated serine protease (MASP)-1-like protein from the Japanese dogfish (Triakis scyllia) suggests the presence of a lectin pathway. The CCP consists of six functionally distinct components: C1n, C2n, C3n, C4n, C8n and C9n, and is activated by immune complexes in the presence of Ca++ and Mg++ ions. The ACP is antibody independent, requiring Mg++ ions and a heat-labile 90 kDa factor B-like protein for activity. Proteins considered homologues of C1q, C3 and C4 (C2n) of the mammalian complement system have been isolated from nurse shark serum. Shark C1q is composed of at least two chain types each showing 50% identity to human C1q chains A and B. Partial sequence of the globular domain of one of the chains shows it to be C1q-like rather than like mannan-binding protein. N-terminal amino acid sequences of the alpha and beta chain of shark C3 and C4 molecules show significant identity with corresponding human C3 and C4 chains. A sequence representing shark C4 gamma chain, shows little similarity to human C4 gamma chain. The terminal shark components C8n and C9n are functional analogues of mammalian C8 and C9. Anaphylatoxin activity has been demonstrated in activated shark serum, and porcine C5a desArg induces shark leucocyte chemotaxis. The deduced amino acid sequence of a partial C3 cDNA clone from the nurse shark shows 50%, 30% and 24% homology with the corresponding region of mammalian C3, C4 and alpha 2-macroglobulin. Deduced amino acid sequence data from partial Bf/C2 cDNA clones, two from the nurse shark and one from the Japanese dogfish, suggest that at least one species of elasmobranch has two distinct Bf/C2 genes.

The Importance of Management in the Deregulated Retail Electricity Distribution Market in Slovenia

OpenAIRE

Drago Papler; Stefan Bojnec

2006-01-01

This paper underlines the importance of management in the deregulated retail electricity distribution market, entrepreneurship and business behaviours toward consumers’ satisfaction with quality of services. The coefficients of concentration indicate a high concentration of electricity suppliers and users in the deregulated electricity retail market for industry. The production function reveals the importance of education and electricity infrastructure, and to a lesser extent of capital inten...

Complement and alcoholic liver disease: role of C1q in the pathogenesis of ethanol-induced liver injury in mice.

Science.gov (United States)

Cohen, Jessica I; Roychowdhury, Sanjoy; McMullen, Megan R; Stavitsky, Abram B; Nagy, Laura E

2010-08-01

Complement is involved in the development of alcoholic liver disease in mice; however, the mechanisms for complement activation during ethanol exposure have not been identified. C1q, the recognition subunit of the first complement component, binds to apoptotic cells, thereby activating the classical complement pathway. Because ethanol exposure increases hepatocellular apoptosis, we hypothesized that ethanol-induced apoptosis would lead to activation of complement via the classical pathway. Wild-type and C1qa-/- mice were allowed free access to ethanol-containing diets or pair-fed control diets for 4 or 25 days. Ethanol feeding for 4 days increased apoptosis of Kupffer cells in both wild-type and C1qa-/- mice. Ethanol-induced deposition of C1q and C3b/iC3b/C3c was colocalized with apoptotic Kupffer cells in wild-type, but not C1qa-/-, mice. Furthermore, ethanol-induced increases in tumor necrosis factor-alpha and interleukin-6 expression at this early time point were suppressed in C1q-deficient mice. Chronic ethanol feeding (25 days) increased steatosis, hepatocyte apoptosis, and activity of serum alanine and aspartate aminotransferases in wild-type mice. These markers of hepatocyte injury were attenuated in C1qa-/- mice. In contrast, chronic ethanol (25 days)-induced increases in cytochrome P450 2E1 expression and oxidative stress did not differ between wild-type and C1qa-/- mice. For the first time, these data indicate that ethanol activates the classical complement pathway via C1q binding to apoptotic cells in the liver and that C1q contributes to the pathogenesis of ethanol-induced liver injury. Copyright (c) 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

Heterocomplexes of mannose-binding lectin and the pentraxins PTX3 or SAP trigger cross-activation of the complement system

DEFF Research Database (Denmark)

Ma, Ying Jie; Doni, Andrea; Skjødt, Mikkel-Ole

2011-01-01

The long pentraxin 3 (PTX3), serum amyloid P component (SAP) and C-reactive protein (CRP) belong to the pentraxin family of pattern recognition molecules involved in tissue homeostasis and innate immunity. They interact with C1q from the classical complement pathway. Whether this also occurs via...... the analogous mannose-binding lectin (MBL) from the lectin complement pathway is unknown. Thus, we investigated the possible interaction between MBL and the pentraxins. We report that MBL bound PTX3 and SAP partly via its collagen-like domain, but not CRP. MBL:PTX3 complex formation resulted in recruitment of C......1q, but this was not seen for the MBL:SAP complex. However, both MBL:PTX3 and MBL:SAP complexes enhanced C4 and C3 deposition and opsonophagocytosis of Candida albicans by polymorphonuclear leukocytes. Interaction between MBL and PTX3 lead to communication between the lectin and classical complement...

Surface-bound capsular polysaccharide of type Ia group B Streptococcus mediates C1 binding and activation of the classic complement pathway

International Nuclear Information System (INIS)

Levy, N.J.; Kasper, D.L.

1986-01-01

The role of surface-bound type Ia group B Streptococcus (GBS) capsular polysaccharide in anti-body-independent binding of C1 and activation of the classic component pathway was investigated. In a radiolabeled bacterial-polymorphonuclear leukocyte (PMN) association assay, a measure of bacterial opsonization, preincubation of 3 H-type Ia GBS with purified F(ab') 2 to the organism blocked the association of the bacteria with PMN', and the inhibitory effect was dose dependent. The specificity of F(ab') 2 blocking was shown after adsorption of F(ab') 2 with type Ia polysaccharide-sensitized erythrocytes. Polysaccharide-adsorbed F(ab') 2 had a 70% decrease in ability to block the association of bacteria with PMN. Neuraminidase digestion removed 80% of the terminal sialic acid residues from the native polysaccharide. These neuraminidase-digested organisms had a 72% decrease in binding and transfer of purified C1 compared with non-enzyme-treated organisms. Type Ia capsular polysaccharide bound to sheep erythrocytes promoted classic complement pathway-mediated hemolysis of the cells. The role of C1 inhibitor (INH) in modulation of C1 activation by the organisms was investigated. The possibility existed that the C1 INH could be bound by the bacteria, allowing C1 activation to occur in the fluid phase. The inhibitor was purified from human serum, and its activity was measured before and after incubation with type Ia GBS. The organisms had no effect on C1 INH activity. Thus surface-bound capsular polysacchardie of type Ia GBS mediates C1 binding and classic pathway activation, and this does not involve the C1 INH

Complement-related proteins control the flavivirus infection of Aedes aegypti by inducing antimicrobial peptides.

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Xiaoping Xiao

2014-04-01

Full Text Available The complement system functions during the early phase of infection and directly mediates pathogen elimination. The recent identification of complement-like factors in arthropods indicates that this system shares common ancestry in vertebrates and invertebrates as an immune defense mechanism. Thioester (TE-containing proteins (TEPs, which show high similarity to mammalian complement C3, are thought to play a key role in innate immunity in arthropods. Herein, we report that a viral recognition cascade composed of two complement-related proteins limits the flaviviral infection of Aedes aegypti. An A. aegypti macroglobulin complement-related factor (AaMCR, belonging to the insect TEP family, is a crucial effector in opposing the flaviviral infection of A. aegypti. However, AaMCR does not directly interact with DENV, and its antiviral effect requires an A. aegypti homologue of scavenger receptor-C (AaSR-C, which interacts with DENV and AaMCR simultaneously in vitro and in vivo. Furthermore, recognition of DENV by the AaSR-C/AaMCR axis regulates the expression of antimicrobial peptides (AMPs, which exerts potent anti-DENV activity. Our results both demonstrate the existence of a viral recognition pathway that controls the flaviviral infection by inducing AMPs and offer insights into a previously unappreciated antiviral function of the complement-like system in arthropods.

Deregulation, market structure and gas prices in the Canadian Natural Gas Industry

International Nuclear Information System (INIS)

Uhler, R.S.

1992-01-01

During the course of the development of the natural gas industry in Canada, gas purchase and sales markets have evolved from being relatively free of regulation to being highly regulated and back again. Though pipeline transport charges were regulated, the pipeline companies, or their subsidiaries, owned the gas that they transported and price and other provisions of purchase and sales contracts were freely negotiated with the producers at one end and distributing utilities or industrial users at the other end. The Western Accord of 1985 set the process of deregulation of the Canadian natural gas industry in motion. On November 1, 1986, natural gas prices in interprovincial trade were deregulated in that domestic natural gas prices were to be freely negotiated. Although not stated explicitly, government policy is to permit export prices to be freely negotiated so long as they do not fall below domestic prices. The deregulation process has dramatically changed the relationship between buyers and sellers. Of particular importance is that deregulation has permitted companies to negotiate gas purchase contracts directly with producers with the pipeline company acting solely as a gas transporter. The purpose of this paper is to examine the forces that have led to shorter term contracts and to examine the likely effect of these contract terms on reservoir development investment incentives. 5 refs., 3 figs

The last chapter in natural gas deregulation? I don't think so

International Nuclear Information System (INIS)

Kirkby, R.G.

1995-01-01

The history of the deregulation of the Canadian gas market was reviewed. Both domestic consumers who did and did not participate in the open gas market, benefited from low costs which were an immediate, highly visible consequence of deregulation. The direct purchase alternative was a major influence in reducing system gas costs. Deregulation also helped to increase Canadian gas exports to the U.S. with the increase in pipeline infrastructure. Ontario's direct purchase environment, characterized by the large number of competitors, has not been without faults. There has been concern about unfair competitive advantages of regulated monopolies. Local gas distributors (LDC) and the competitive advantages they enjoy, were discussed. The LDC was characterized as a monopoly gas distributor and a gas merchant at the same time. Possible solutions to this problem were presented. It was suggested that the LDC, as a gas merchant, should be required to facilitate development of the competitive market rather than compete in it. An alternative was to separate the distribution and merchant functions. A third option was to require that LDCs relinquish their gas merchant role along the lines similar to what has taken place in the USA on interstate pipelines, and to a more limited extent, in Quebec. In the opinion of this speaker any solution in the near future would not be the last step in establishing complete deregulation. 3 figs

U.S. Banking Deregulation and Emerging Market Loans: Potential Links and Evidence, 1984~2005

Directory of Open Access Journals (Sweden)

Hyun Koo Cho

2010-06-01

Full Text Available How did the deregulation of U.S. bank activities affect the patterns of cross-border lending to emerging economies? Unlike bank lending from Europe or Japan, U.S. bank lending to emerging economies exhibited increasing volatility over time. Using U.S. cross-border bank exposure data, this study identifies a temporal association between important deregulation initiatives and the volatility of U.S. bank emerging market lending. This association is explained by the linkages between an important outcome of bank deregulation－earnings volatility from diversified bank activities－and the rising volatility. Together, it argues that U.S. banking deregulation had unanticipated effects of exacerbating the volatility of bank lending to emerging economies.

microRNA dependent and independent deregulation of long non-coding RNAs by an oncogenic herpesvirus.

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Sunantha Sethuraman

2017-07-01

Full Text Available Kaposi's sarcoma (KS is a highly prevalent cancer in AIDS patients, especially in sub-Saharan Africa. Kaposi's sarcoma-associated herpesvirus (KSHV is the etiological agent of KS and other cancers like Primary Effusion Lymphoma (PEL. In KS and PEL, all tumors harbor latent KSHV episomes and express latency-associated viral proteins and microRNAs (miRNAs. The exact molecular mechanisms by which latent KSHV drives tumorigenesis are not completely understood. Recent developments have highlighted the importance of aberrant long non-coding RNA (lncRNA expression in cancer. Deregulation of lncRNAs by miRNAs is a newly described phenomenon. We hypothesized that KSHV-encoded miRNAs deregulate human lncRNAs to drive tumorigenesis. We performed lncRNA expression profiling of endothelial cells infected with wt and miRNA-deleted KSHV and identified 126 lncRNAs as putative viral miRNA targets. Here we show that KSHV deregulates host lncRNAs in both a miRNA-dependent fashion by direct interaction and in a miRNA-independent fashion through latency-associated proteins. Several lncRNAs that were previously implicated in cancer, including MEG3, ANRIL and UCA1, are deregulated by KSHV. Our results also demonstrate that KSHV-mediated UCA1 deregulation contributes to increased proliferation and migration of endothelial cells.

The role of complement in CD4⁺ T cell homeostasis and effector functions.

Science.gov (United States)

Kolev, Martin; Le Friec, Gaëlle; Kemper, Claudia

2013-02-01

The complement system is among the evolutionary oldest 'players' of the immune system. It was discovered in 1896 by Jules Bordet as a heat-labile fraction of the serum responsible for the opsonisation and subsequent killing of bacteria. The decades between the 1920s and 1990s then marked the discovery and biochemical characterization of the proteins comprising the complement system. Today, complement is defined as a complex system consisting of more than 30 membrane-bound and soluble plasma proteins, which are activated in a cascade-like manner, very similarly to the caspase proteases and blood coagulation systems. Complement is engrained in the immunologist's mind as a serum-effective, quintessential part of innate immunity, vitally required for the detection and removal of pathogens or other dangerous entities. Three decades ago, this rather confined definition was challenged and then refined when it was shown that complement participates vitally in the induction and regulation of B cell responses, thus adaptive immunity. Similarly, research work published in more recent years supports an equally important role for the complement system in shaping T cell responses. Today, we are again facing paradigm shifts in the field: complement is actively involved in the negative control of T cell effector immune responses, and thus, by definition in immune homeostasis. Further, while serum complement activity is without doubt fundamental in the defence against invading pathogens, local immune cell-derived production of complement emerges as key mediator of complement's impact on adaptive immune responses. And finally, the impact of complement on metabolic pathways and the crosstalk between complement and other immune effector systems is likely more extensive than previously anticipated and is fertile ground for future discoveries. In this review, we will discuss these emerging new roles of complement, with a focus on Th1 cell biology. Copyright © 2013 Elsevier Ltd. All

Yersinia enterocolitica serum resistance proteins YadA and ail bind the complement regulator C4b-binding protein.

Directory of Open Access Journals (Sweden)

Vesa Kirjavainen

Full Text Available Many pathogens are equipped with factors providing resistance against the bactericidal action of complement. Yersinia enterocolitica, a Gram-negative enteric pathogen with invasive properties, efficiently resists the deleterious action of human complement. The major Y. enterocolitica serum resistance determinants include outer membrane proteins YadA and Ail. Lipopolysaccharide (LPS O-antigen (O-ag and outer core (OC do not contribute directly to complement resistance. The aim of this study was to analyze a possible mechanism whereby Y. enterocolitica could inhibit the antibody-mediated classical pathway of complement activation. We show that Y. enterocolitica serotypes O:3, O:8, and O:9 bind C4b-binding protein (C4bp, an inhibitor of both the classical and lectin pathways of complement. To identify the C4bp receptors on Y. enterocolitica serotype O:3 surface, a set of mutants expressing YadA, Ail, O-ag, and OC in different combinations was tested for the ability to bind C4bp. The studies showed that both YadA and Ail acted as C4bp receptors. Ail-mediated C4bp binding, however, was blocked by the O-ag and OC, and could be observed only with mutants lacking these LPS structures. C4bp bound to Y. enterocolitica was functionally active and participated in the factor I-mediated degradation of C4b. These findings show that Y. enterocolitica uses two proteins, YadA and Ail, to bind C4bp. Binding of C4bp could help Y. enterocolitica to evade complement-mediated clearance in the human host.

Modulatory Role of Surface Coating of Superparamagnetic Iron Oxide Nanoworms in Complement Opsonization and Leukocyte Uptake

DEFF Research Database (Denmark)

Inturi, Swetha; Wang, Guankui; Chen, Fangfang

2015-01-01

demonstrated that neutrophils, monocytes, lymphocytes and eosinophils took up SPIO NWs, and the uptake was prevented by EDTA (a general complement inhibitor) and by antiproperdin antibody (an inhibitor of the alternative pathway of the complement system). Cross-linking and hydrogelation of SPIO NWs surface...... by epichlorohydrin decreased C3 opsonization in mouse serum, and consequently reduced the uptake by mouse leukocytes by more than 70% in vivo. Remarkably, the cross-linked particles did not show a decrease in C3 opsonization in human serum, but showed a significant decrease (over 60%) of the uptake by human...... leukocytes. The residual uptake of cross-linked nanoparticles was completely blocked by EDTA. These findings demonstrate species differences in complement-mediated nanoparticle recognition and uptake by leukocytes, and further show that human hemocompatibility could be improved by inhibitors of complement...

Productivity growth and deregulation of Japanese electricity distribution

International Nuclear Information System (INIS)

Goto, Mika; Sueyoshi, Toshiyuki

2009-01-01

Deregulation of Japanese electric power industry began in 1995. After the amendment of Electricity Utility Industry Law in 1995, competition was partially introduced in a generation sector and retail competition started from 2000. Eligibility to choose suppliers was gradually extended from larger to smaller customers. As of 2008, almost all customers except households can choose their electricity suppliers. Based upon both previous implementation result of competition policy and review on their achievement, Japanese government will begin new policy debate in 2013 to assess further retail competition which includes household customers. To prepare for policy suggestion on the future electric power industry, this study examines the cost structure of Japanese electricity distribution. For the purpose, we estimate a multi-product translog cost function of Japanese electricity distribution from 1983 to 2003. Using the estimated cost function, we calculate several economic measures such as productivity growth, technical change and economies of scale and scope. The empirical results of this study indicate the improvement in productivity growth after deregulation.

The alternative complement pathway control protein H binds to immune complexes and serves their detection

International Nuclear Information System (INIS)

Nydegger, U.E.; Corvetta, A.; Spaeth, P.J.; Spycher, M.

1983-01-01

During solubilization of immune complexes C3b becomes fixed to the immunoglobulin part and serves as a receptor for the alternative complement pathway control protein H. The H-C3b immune complex interaction can be made detectable using 4% polyethyleneglycol to separate free from bound 125 I-H. Tetanus toxoid (Te)/anti-Te complexes kept soluble with fresh serum and containing 125 IU of specific antibody bound 18% of 125 I-H; when fresh serum was chelated with 10 mM EDTA, 125 I-H binding was only 5%. On sucrose density gradients, the H-binding material sedimented in the range of 12 to 30 S. In 36 serum samples from rheumatoid arthritis (RA) patients and in 12 serum samples from patients with systemic lupus erythematosus (SLE), 125 I-H binding was significantly elevated to 9.5 +/- 4.7% (mean +/- 1 SD) and 13.3 +/- 5.6%, respectively, while 125 I-H binding by 36 normal human sera was 4 +/- 2%. RA samples (17/36, 47%) and SLE samples (9/12, 75%) had H-binding values increased by more than 2 SD above the normal mean. The serum samples were also assessed for conglutinin- and C1q-binding activities; a significant correlation between H and C1q binding was observed (P less than 0.001); there was no correlation between H and conglutinin binding. Although binding to immune complexes through its interaction with C3b, H clearly detects a population of complexes other than conglutinin, thus expanding the possibilities of further characterizing pathological complexes

TCSC based automatic generation control of deregulated power system using quasi-oppositional harmony search algorithm

Directory of Open Access Journals (Sweden)

Mahendra Nandi

2017-08-01

Full Text Available In present aspect, automatic generation control (AGC of deregulated power system with thyristor controlled series compensator (TCSC device is investigated. The objective is to discuss bilateral power transaction issue with the TCSC effect. A deregulated two-area power system model having two thermal units in each control area is considered for this act. A quasi-oppositional harmony search (QOHS algorithm is being applied for the constrained optimization problem. Three cases, commonly studied in deregulation, are discussed for the effectiveness of the proposed technique. Further, sensitivity analysis is studied by varying the test system parameters up to ±25% from their rated values. The obtained simulation plots are analytically discussed with the calculation of oscillatory modes, transient details and the studied performance indices. Sugeno fuzzy logic control technique is also investigated to the studied test system. The simulation results show that the proposed QOHS based TCSC controller is quite effective in deregulated environment.

Integration of multiple networks and pathways identifies cancer driver genes in pan-cancer analysis.

Science.gov (United States)

Cava, Claudia; Bertoli, Gloria; Colaprico, Antonio; Olsen, Catharina; Bontempi, Gianluca; Castiglioni, Isabella

2018-01-06

Modern high-throughput genomic technologies represent a comprehensive hallmark of molecular changes in pan-cancer studies. Although different cancer gene signatures have been revealed, the mechanism of tumourigenesis has yet to be completely understood. Pathways and networks are important tools to explain the role of genes in functional genomic studies. However, few methods consider the functional non-equal roles of genes in pathways and the complex gene-gene interactions in a network. We present a novel method in pan-cancer analysis that identifies de-regulated genes with a functional role by integrating pathway and network data. A pan-cancer analysis of 7158 tumour/normal samples from 16 cancer types identified 895 genes with a central role in pathways and de-regulated in cancer. Comparing our approach with 15 current tools that identify cancer driver genes, we found that 35.6% of the 895 genes identified by our method have been found as cancer driver genes with at least 2/15 tools. Finally, we applied a machine learning algorithm on 16 independent GEO cancer datasets to validate the diagnostic role of cancer driver genes for each cancer. We obtained a list of the top-ten cancer driver genes for each cancer considered in this study. Our analysis 1) confirmed that there are several known cancer driver genes in common among different types of cancer, 2) highlighted that cancer driver genes are able to regulate crucial pathways.

Rivaroxaban limits complement activation compared with warfarin in antiphospholipid syndrome patients with venous thromboembolism.

Science.gov (United States)

Arachchillage, D R J; Mackie, I J; Efthymiou, M; Chitolie, A; Hunt, B J; Isenberg, D A; Khamashta, M; Machin, S J; Cohen, H

2016-11-01

Essentials Complement activation has a pathogenic role in thrombotic antiphospholipid syndrome (APS). Coagulation proteases such as factor Xa can activate complement proteins. Complement activation markers were elevated in anticoagulated thrombotic APS patients. Complement activation decreased in APS patients switching from warfarin to rivaroxaban. Background Complement activation may play a major role in the pathogenesis of thrombotic antiphospholipid syndrome (APS). Coagulation proteases such as factor Xa can activate complement proteins. Aims To establish whether rivaroxaban, a direct factor Xa inhibitor, limits complement activation compared with warfarin in APS patients with previous venous thromboembolism (VTE). Methods A total of 111 APS patients with previous VTE, on warfarin target INR 2.5, had blood samples taken at baseline and at day 42 after randomization in the RAPS (Rivaroxaban in Antiphospholipid Syndrome) trial. Fifty-six patients remained on warfarin and 55 switched to rivaroxaban. Fifty-five normal controls (NC) were also studied. Markers of complement activation (C3a, C5a, terminal complement complex [SC5b-9] and Bb fragment) were assessed. Results APS patients had significantly higher complement activation markers compared with NC at both time-points irrespective of the anticoagulant. There were no differences between the two patient groups at baseline, or patients remaining on warfarin at day 42. In 55 patients randomized to rivaroxaban, C3a, C5a and SC5b-9 were lower at day 42 (median (ng mL -1 ) [confidence interval] 64 [29-125] vs. 83 [35-147], 9 [2-15] vs. 12 [4-18] and 171 [56-245] vs. 201 [66-350], respectively) but levels of Bb fragment were unchanged. There were no correlations between rivaroxaban levels and complement activation markers. Conclusions APS patients with previous VTE on warfarin exhibit increased complement activation, which is likely to occur via the classical pathway and is decreased by rivaroxaban administration

Analysis of deregulation models; Denryoku shijo jiyuka model no bunseki

Energy Technology Data Exchange (ETDEWEB)

Yajima, M. [Central Research Institute of Electric Power Industry, Tokyo (Japan)

1996-04-01

Trends toward power market deregulation were investigated in Japan and 16 other countries, and various deregulation models were examined and evaluated for their merits and demerits. There are four basic models, that is, franchise bidding model, competitive bidding in power generation model, wholesale wheeling or retail wheeling model, and mandatory pool or voluntary pool model. Power market deregulation has been a global tendency since the second half of the 1970s, with various models adopted by different countries. Out of the above-said models, it is the retail wheeling model and pool models (open access models) that allow the final customer to select power suppliers, and the number of countries adopting these models is increasing. The said models are characterized in that the disintegration of the vertical transmission-distribution integration (separation of distribution service and retail supply service) and the liberation of the retail market are simultaneously accomplished. The pool models, in particular, are enjoying favor because conditions for fair competition have already been prepared and because it is believed high in efficiency. In Japan and France, where importance is attached to atomic power generation, the competitive bidding model is adopted as a means to harmonize the introduction of competition into the source development and power generation sectors. 7 refs., 4 tabs.

Change in consumer sensitivity to electricity prices in response to retail deregulation: A panel empirical analysis of the residential demand for electricity in the United States

International Nuclear Information System (INIS)

Nakajima, Tadahiro; Hamori, Shigeyuki

2010-01-01

About ten years have passed since the deregulation of the U.S. retail electricity market, and it is now generally accepted that the available data is adequate to quantitatively assess and compare conditions before and after deregulation. This study, therefore, estimates the changes in price elasticity in the residential electricity market to examine the changes, if any, in household sensitivity (as a result of retail electricity market deregulation policies) to residential electricity rates. Specifically, six types of panel data are prepared, based on three cross-sections-all states (except for Alaska and Hawaii) and the District of Columbia, deregulated states, and non-deregulated states-and two time series-the period before deregulation and the period after deregulation. The panel empirical analysis techniques are used to determine whether or not the variables are stationary, and to estimate price elasticity. We find that there is no substantial difference in the price elasticity between deregulated and non-deregulated states for both periods-before deregulation and after deregulation. Thus, it can be said that the deregulation of the retail electricity market has not made consumers more sensitive to electricity rates and that retail deregulation policies are not the cause of price elasticity differences between deregulated and non-deregulated states.

Change in consumer sensitivity to electricity prices in response to retail deregulation. A panel empirical analysis of the residential demand for electricity in the United States

Energy Technology Data Exchange (ETDEWEB)

Nakajima, Tadahiro [The Kansai Electric Power Company, Incorporated, 6-16, Nakanoshima 3-chome, Kita-Ku, Osaka 530-8270 (Japan); Hamori, Shigeyuki [Faculty of Economics, Kobe University 2-1, Rokkodai, Nada-Ku, Kobe 657-8501 (Japan)

2010-05-15

About ten years have passed since the deregulation of the U.S. retail electricity market, and it is now generally accepted that the available data is adequate to quantitatively assess and compare conditions before and after deregulation. This study, therefore, estimates the changes in price elasticity in the residential electricity market to examine the changes, if any, in household sensitivity (as a result of retail electricity market deregulation policies) to residential electricity rates. Specifically, six types of panel data are prepared, based on three cross-sections - all states (except for Alaska and Hawaii) and the District of Columbia, deregulated states, and non-deregulated states - and two time series - the period before deregulation and the period after deregulation. The panel empirical analysis techniques are used to determine whether or not the variables are stationary, and to estimate price elasticity. We find that there is no substantial difference in the price elasticity between deregulated and non-deregulated states for both periods - before deregulation and after deregulation. Thus, it can be said that the deregulation of the retail electricity market has not made consumers more sensitive to electricity rates and that retail deregulation policies are not the cause of price elasticity differences between deregulated and non-deregulated states. (author)

Complement System in the Pathogenesis of Benign Lymphoepithelial Lesions of the Lacrimal Gland.

Directory of Open Access Journals (Sweden)

Jing Li

Full Text Available We aimed to examine the potential involvement of local complement system gene expression in the pathogenesis of benign lymphoepithelial lesions (BLEL of the lacrimal gland.We collected data from 9 consecutive pathologically confirmed patients with BLEL of the lacrimal gland and 9 cases with orbital cavernous hemangioma as a control group, and adopted whole genome microarray to screen complement system-related differential genes, followed by RT-PCR verification and in-depth enrichment analysis (Gene Ontology analysis of the gene sets.The expression of 14 complement system-related genes in the pathologic tissue, including C2, C3, ITGB2, CR2, C1QB, CR1, ITGAX, CFP, C1QA, C4B|C4A, FANCA, C1QC, C3AR1 and CFHR4, were significantly upregulated while 7 other complement system-related genes, C5, CFI, CFHR1|CFH, CFH, CD55, CR1L and CFD were significantly downregulated in the lacrimal glands of BLEL patients. The microarray results were consistent with RT-PCR analysis results. Immunohistochemistry analysis of C3c and C1q complement component proteins in the resected tissue were positive in BLEL patients, while the control group had negative expression of these proteins. Gene ontology (GO analysis revealed that activation of the genes of complement system-mediated signaling pathways were the most enriched differential gene group in BLEL patients.Local expression of complement components is prominently abnormal in BLEL, and may well play a role in its pathogenesis.

Nuclear regulation on the electrical sector's deregulation horizon

International Nuclear Information System (INIS)

Kindelan, J.M.

1997-01-01

The electrical sector is generally tending towards a deregulated system which will exert greater pressure on production costs. The author uses this article to reflect on the consequences this new conception will bring for nuclear energy and, particularly, for the activity of regulatory agencies and safety requirements. (Author)

A NEPOTISM AND CRONY IN A BUSINESS, CASE OF INDUSTRIAL DEREGULATION IN INDONESIA

Directory of Open Access Journals (Sweden)

Muhadjir Efendy

2011-06-01

Full Text Available An industrial deregulation is a government policy in developing a state’s economic infrastructure. If a country undergoes a process of powerful personalization, its interest is identical with a powerful interest. For an economic profit, the President’s relative and crony do a business and build directly unproductive seeking activities. This study aims to examine the relation of relative to crony in realizing an industrial deregulation in the 1980s and its impact on the Indonesian economy in a view of macroeconomic policy. It focuses on a problem of the industrial deregulation from 1983 to 1990 with economic growth by the indicator of contribution to GDP and labor force. The study used an expose facto approach. The data were the secondary sources: documents, textbooks and mass media. It used a qualitative-descriptive analysis.

Signaling pathway deregulation and molecular alterations across pediatric medulloblastomas.

Science.gov (United States)

Lhermitte, B; Blandin, A F; Coca, A; Guerin, E; Durand, A; Entz-Werlé, N

2018-05-15

Medulloblastomas (MBs) account for 15% of brain tumors in children under the age of 15. To date, the overall 5-year survival rate for all children is only around 60%. Recent advances in cancer genomics have led to a fundamental change in medulloblastoma classification and is evolving along with the genomic discoveries, allowing to regularly reclassify this disease. The previous molecular classification defined 4 groups (WNT-activated MB, SHH-activated MB and the groups 3 and 4 characterized partially by NMYC and MYC driven MBs). This stratification moved forward recently to better define these groups and their correlation to outcome. This new stratification into 7 novel subgroups was helpful to lay foundations and complementary data on the understanding regarding molecular pathways and gene mutations underlying medulloblastoma biology. This review was aimed at answering the recent key questions on MB genomics and go further in the relevance of those genes in MB development as well as in their targeted therapies. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Parental genome dosage imbalance deregulates imprinting in Arabidopsis.

Directory of Open Access Journals (Sweden)

Pauline E Jullien

2010-03-01

Full Text Available In mammals and in plants, parental genome dosage imbalance deregulates embryo growth and might be involved in reproductive isolation between emerging new species. Increased dosage of maternal genomes represses growth while an increased dosage of paternal genomes has the opposite effect. These observations led to the discovery of imprinted genes, which are expressed by a single parental allele. It was further proposed in the frame of the parental conflict theory that parental genome imbalances are directly mirrored by antagonistic regulations of imprinted genes encoding maternal growth inhibitors and paternal growth enhancers. However these hypotheses were never tested directly. Here, we investigated the effect of parental genome imbalance on the expression of Arabidopsis imprinted genes FERTILIZATION INDEPENDENT SEED2 (FIS2 and FLOWERING WAGENINGEN (FWA controlled by DNA methylation, and MEDEA (MEA and PHERES1 (PHE1 controlled by histone methylation. Genome dosage imbalance deregulated the expression of FIS2 and PHE1 in an antagonistic manner. In addition increased dosage of inactive alleles caused a loss of imprinting of FIS2 and MEA. Although FIS2 controls histone methylation, which represses MEA and PHE1 expression, the changes of PHE1 and MEA expression could not be fully accounted for by the corresponding fluctuations of FIS2 expression. Our results show that parental genome dosage imbalance deregulates imprinting using mechanisms, which are independent from known regulators of imprinting. The complexity of the network of regulations between expressed and silenced alleles of imprinted genes activated in response to parental dosage imbalance does not support simple models derived from the parental conflict hypothesis.

Market Power of Local Cable Television Franchises: Evidence from the Effects of Deregulation

OpenAIRE

Adam B. Jaffe; David M. Kanter

1990-01-01

The 1989 Cable Act eliminated most price regulation of cable television operators, including the right of municipalities to enforce price terms in franchise agreements. Deregulation was justified, at least partially, by the contention that competition from other entertainment media eliminated any market power of cable franchises. We examine the value at sale of existing cable systems before and after deregulation. Assuming that this value represents the expected present value of future profit...

Control of the classical and the MBL pathway of complement activation

DEFF Research Database (Denmark)

Petersen, Steen Vang; Thiel, S; Jensen, L

2000-01-01

and the influence of high ionic strength on the complexes indicate that the activation and control of the MBL pathway differ from that of the classical pathway. MBL deficiency is linked to various clinical manifestations such as recurrent infections, severe diarrhoea, and recurrent miscarriage. On the other hand...... incubation at 37 degrees C in physiological buffer, the associated inhibitors as well as MASP-1, MASP-2, and MAp19 dissociated from MBL, whereas only little dissociation of the complex occurred in buffer with high ionic strength (1 M NaCl). The difference in sensitivity to various inhibitors...

The membrane attack complex of the complement system is essential for rapid wallerian degeneration

NARCIS (Netherlands)

Ramaglia, Valeria; King, Rosalind Helen Mary; Nourallah, Michelle; Wolterman, Ruud; de Jonge, Rosalein; Ramkema, Marja; Vigar, Miriam Ann; van der Wetering, Sandra; Morgan, Brian Paul; Troost, Dirk; Baas, Frank

2007-01-01

The complement (C) system plays an important role in myelin breakdown during Wallerian degeneration (WD). The pathway and mechanism involved are, however, not clear. In a crush injury model of the sciatic nerve, we show that C6, necessary for the assembly of the membrane attack complex (MAC), is

Power systems locational marginal pricing in deregulated markets

Science.gov (United States)

Wang, Hui-Fung Francis

Since the beginning of the 1990s, the electricity business is transforming from a vertical integrating business to a competitive market operations. The generation, transmission, distribution subsystem of an electricity utility are operated independently as Genco (generation subsystem), Transco (transmission subsystem), and Distco (distribution subsystem). This trend promotes more economical inter- and intra regional transactions to be made by the participating companies and the users of electricity to achieve the intended objectives of deregulation. There are various types of electricity markets that are implemented in the North America in the past few years. However, transmission congestion management becomes a key issue in the electricity market design as more bilateral transactions are traded across long distances competing for scarce transmission resources. It directly alters the traditional concept of energy pricing and impacts the bottom line, revenue and cost of electricity, of both suppliers and buyers. In this research, transmission congestion problem in a deregulated market environment is elucidated by implementing by the Locational Marginal Pricing (LMP) method. With a comprehensive understanding of the LMP method, new mathematical tools will aid electric utilities in exploring new business opportunities are developed and presented in this dissertation. The dissertation focuses on the development of concept of (LMP) forecasting and its implication to the market participants in deregulated market. Specifically, we explore methods of developing fast LMP calculation techniques that are differ from existing LMPs. We also explore and document the usefulness of the proposed LMP in determining electricity pricing of a large scale power system. The developed mathematical tools use of well-known optimization techniques such as linear programming that are support by several flow charts. The fast and practical security constrained unit commitment methods are the

Do acquisitions by electric utility companies create value? Evidence from deregulated markets

International Nuclear Information System (INIS)

Kishimoto, Jo; Goto, Mika; Inoue, Kotaro

2017-01-01

In the early 1990s, the United Kingdom (the UK) initiated widespread reforms in the electricity industry through a series of market liberalization policies. Several other countries have subsequently followed the lead and restructured their electricity industry. A major outcome of the deregulation effort is the spate of takeovers, both domestic and global, by electric utility companies. With the entry of new players and increasing competition, the business environment of the electricity industry has changed dramatically. This study analyzes the economic impact of mergers and acquisitions (M&As) in the electric utility industry after deregulation. We have examined acquisitions that took place between 1998 and 2013 in the United States, Canada, the UK, Germany, and France. Although previous studies showed no evidence of a positive effect on acquiring firms through M&As, we find that acquisitions by electric utility companies increased the acquiring firms’ share value and improved their operating performance, primarily through efficiency gains after the deregulation. These results are consistent with the empirical evidence and implications presented by Andrade et al. (2001) that M&A created value for the shareholders of the acquiring and target combined firms. - Highlights: • This study examined mergers and acquisitions (M&A) in electric utility industry. • The sample covered M&A between 1998 and 2013 in North America and Europe. • We found M&A significantly increased acquiring firms’ share value and operating performance. • Deregulation policy realized gains for shareholders without incurring costs for consumers.

Complementing the sugar code: role of GAGs and sialic acid in complement regulation

Directory of Open Access Journals (Sweden)

Alex eLangford-Smith

2015-02-01

Full Text Available Sugar molecules play a vital role on both microbial and mammalian cells, where they are involved in cellular communication, govern microbial virulence and modulate host immunity and inflammatory responses. The complement cascade, as part of a host’s innate immune system, is a potent weapon against invading bacteria but has to be tightly regulated to prevent inappropriate attack and damage to host tissues. A number of complement regulators, such as factor H and properdin, interact with sugar molecules, such as glycosaminoglycans and sialic acid, on host and pathogen membranes and direct the appropriate complement response by either promoting the binding of complement activators or inhibitors. The binding of these complement regulators to sugar molecules can vary from location to location, due to their different specificities and because distinct structural and functional subpopulations of sugars are found in different human organs, such as the brain, kidney and eye. This review will cover recent studies that have provided important new insights into the role of glycosaminoglycans and sialic acid in complement regulation and how sugar recognition may be compromised in disease

Complement Activation in Inflammatory Skin Diseases

Directory of Open Access Journals (Sweden)

Jenny Giang

2018-04-01

Full Text Available The complement system is a fundamental part of the innate immune system, playing a crucial role in host defense against various pathogens, such as bacteria, viruses, and fungi. Activation of complement results in production of several molecules mediating chemotaxis, opsonization, and mast cell degranulation, which can contribute to the elimination of pathogenic organisms and inflammation. Furthermore, the complement system also has regulating properties in inflammatory and immune responses. Complement activity in diseases is rather complex and may involve both aberrant expression of complement and genetic deficiencies of complement components or regulators. The skin represents an active immune organ with complex interactions between cellular components and various mediators. Complement involvement has been associated with several skin diseases, such as psoriasis, lupus erythematosus, cutaneous vasculitis, urticaria, and bullous dermatoses. Several triggers including auto-antibodies and micro-organisms can activate complement, while on the other hand complement deficiencies can contribute to impaired immune complex clearance, leading to disease. This review provides an overview of the role of complement in inflammatory skin diseases and discusses complement factors as potential new targets for therapeutic intervention.

Deregulation and growth in China's energy sector: a review of recent development

International Nuclear Information System (INIS)

Wu, Yanrui.

2003-01-01

Dramatic changes have taken place in China's energy sector over the past decade. These changes have important implications for energy consumption, trade, production and regulatory policies in China and beyond. The objective of this paper is to review some of the key issues associated with deregulation and growth in China's energy sector. Specifically, the paper presents a survey of recent reforms in this sector; it also analyses the impact of deregulation on energy policy, ownership, foreign investment and trade, and sheds some lights on the sources of growth in China's energy sector

Generation capacity issues in deregulated markets : a Canadian perspective, volume 1

International Nuclear Information System (INIS)

Ayres, M.; Brereton, B.; Czamanski, D.; Van Melle, B.; Penman, A.

2004-01-01

A study was conducted by the Canadian Energy Research Institute (CERI) to assess generation capacity issues in deregulated electricity markets in Canada. This first volume is based on observations of the restructuring experience in several jurisdictions. It describes how, or if, energy-only markets are succeeding in ensuring capacity additions, and under what conditions. Supply-side and demand-side mechanisms have been proposed as solutions to address these problems. The report focuses on theoretical and practical issues of adequacy that are most relevant from a Canadian perspective. In fully developed energy markets, the price of energy reflects scarcity. Prices are low when generating resources are abundant, and owners make investment decisions based on price expectations. Although deregulated markets may theoretically offer a solution to the capacity adequacy problem, experience has shown that it is not easy to make the rules that make markets operate efficiently. It was concluded that it seems unlikely that deregulated markets in their current state will be able to offer adequate generation for the long term. The challenge lies in moving to competitive markets that encourage long term investment, and adding a capacity mechanism to the market design. refs., tabs., figs

Competing in a fully deregulated market

International Nuclear Information System (INIS)

Bengtsson, A.; Schoen, G.; Johansson, B.

1999-01-01

Vattenfall, Sweden's largest utility, has provided competitively priced nuclear electricity to a price-conscious market for several decades. As Sweden is an exporting country, the cost of products must be kept as low as possible to meet tough European competition. Since Sweden relies almost exclusively on electricity for energy, electric prices must be low to keep Swedish products competitive. Because of the available hydropower in Sweden and Norway, nuclear power plants have been forced to operate with high availability and low cost. From the first years after nuclear plants began operation, there has been a continuous development of organization, management, and work practices to sustain low-cost production. Now, the European electricity market is undergoing deregulation and open competition. This is taking place in a situation where the increase in demand is relatively weak and where the availability of generation capacity is good. Sweden is at the forefront of the competition. According to the well-known law of supply and demand, this entails the risk of squeezed prices, but the situation also offers many opportunities for those making the right decisions. The availability of electricity at competitive prices has great significance for the competitiveness of the industry in general and for the electricity-intensive industry in particular. If the customer then, in a deregulated market is free to choose the supplier, the focus definitely is on the customer

Selling power : marketing energy under deregulation

Energy Technology Data Exchange (ETDEWEB)

Drummond, J.; Hanna, F.

2001-07-01

This book discussed the marketing of energy in a deregulated environment. Experience from long distance telephone service providers has shown that historical dominance is not a guarantee for future success. As new brands are introduced and as consumer choice increases, so does the ability to change from one provider to another. Price is only one of the factors prompting that change. Old rules and practices do not bind new competitors who must face the challenge of open competition and must be aware of the ever-changing face of business. It was recommended that the strategic solution would be to build a brand and to develop significant market shares and create effective customer retention programs. This book focused on the elements that energy marketing professionals must use to maintain and increase share without product differentiation. It also explained how energy providers can effectively attract and retain customers over the long term while keeping marketing and service delivery costs down. It was suggested that small players can compete with the growing strength of regional providers by creating new alliances between larger energy conglomerates. The chapters of the book were entitled: (1) Introduction, (2) The Goals of Deregulation, (3) Strategic Marketing Choices, (4) Relationship Marketing, (5) The Role of Customer Service, (6) The Question of Outsourcing, and (7) Final Thoughts and Observations. 24 refs., 3 figs.

Selling power : marketing energy under deregulation

International Nuclear Information System (INIS)

Drummond, J.; Hanna, F.

2001-01-01

This book discussed the marketing of energy in a deregulated environment. Experience from long distance telephone service providers has shown that historical dominance is not a guarantee for future success. As new brands are introduced and as consumer choice increases, so does the ability to change from one provider to another. Price is only one of the factors prompting that change. Old rules and practices do not bind new competitors who must face the challenge of open competition and must be aware of the ever-changing face of business. It was recommended that the strategic solution would be to build a brand and to develop significant market shares and create effective customer retention programs. This book focused on the elements that energy marketing professionals must use to maintain and increase share without product differentiation. It also explained how energy providers can effectively attract and retain customers over the long term while keeping marketing and service delivery costs down. It was suggested that small players can compete with the growing strength of regional providers by creating new alliances between larger energy conglomerates. The chapters of the book were entitled: (1) Introduction, (2) The Goals of Deregulation, (3) Strategic Marketing Choices, (4) Relationship Marketing, (5) The Role of Customer Service, (6) The Question of Outsourcing, and (7) Final Thoughts and Observations. 24 refs., 3 figs

Network industries deregulation and energy industries reorganization

International Nuclear Information System (INIS)

Delaporte, P.; Chevalier, J.M.; Bourdaire, J.M.

1999-01-01

The electric power distribution systems deregulation is going to change the economical and institutional scenery. The empowerment term can be anything but a happy change for the customer by giving him the free choice. But this evolution calls the public power in question again. Meanwhile the government has to remain vigilant and watch over the safety in terms of cartel and environment risk. (A.L.B.)

Optimal electricity price calculation model for retailers in a deregulated market

Energy Technology Data Exchange (ETDEWEB)

Yusta, J.M.; Dominguez-Navarro, J.A. [Zaragoza Univ., Dept. of Electrical Engineering, Zaragoza (Spain); Ramirez-Rosado, I.J. [La Rioja Univ., Dept. of Electrical Engineering, Logrono (Spain); Perez-Vidal, J.M. [McKinnon and Clarke, Energy Services Div., Zaragoza (Spain)

2005-07-01

The electricity retailing, a new business in deregulated electric power systems, needs the development of efficient tools to optimize its operation. This paper defines a technical-economic model of an electric energy service provider in the environment of the deregulated electricity market in Spain. This model results in an optimization problem, for calculating the optimal electric power and energy selling prices that maximize the economic profits obtained by the provider. This problem is applied to different cases, where the impact on the profits of several factors, such as the price strategy, the discount on tariffs and the elasticity of customer demand functions, is studied. (Author)

Optimal electricity price calculation model for retailers in a deregulated market

International Nuclear Information System (INIS)

Yusta, J.M.; Dominguez-Navarro, J.A.; Ramirez-Rosado, I.J.; Perez-Vidal, J.M.

2005-01-01

The electricity retailing, a new business in deregulated electric power systems, needs the development of efficient tools to optimize its operation. This paper defines a technical-economic model of an electric energy service provider in the environment of the deregulated electricity market in Spain. This model results in an optimization problem, for calculating the optimal electric power and energy selling prices that maximize the economic profits obtained by the provider. This problem is applied to different cases, where the impact on the profits of several factors, such as the price strategy, the discount on tariffs and the elasticity of customer demand functions, is studied. (Author)

The deregulation effects of Finnish electricity markets on district heating prices

International Nuclear Information System (INIS)

Linden, Mikael; Peltola-Ojala, Paeivi

2010-01-01

This paper investigates an empirical econometric panel data model in order to test deregulation and regional market structure effects on district heating prices in Finland for period 1996-2002. The data was collected from 76 district heating firms throughout Finland. Special emphasis is placed on the modeling of policy-induced competition, which began in year 1999, regional based fuel selection, local market structures, and distribution network sharing effects. The results imply that the local structures of energy production and sales have an important role to play in the formation of market prices and that the price lowering effects of energy market deregulation are permanent. (author)

CovR Regulates Streptococcus mutans Susceptibility To Complement Immunity and Survival in Blood

Science.gov (United States)

Alves, Lívia A.; Nomura, Ryota; Mariano, Flávia S.; Harth-Chu, Erika N.; Stipp, Rafael N.; Nakano, Kazuhiko

2016-01-01

Streptococcus mutans, a major pathogen of dental caries, may promote systemic infections after accessing the bloodstream from oral niches. In this study, we investigate pathways of complement immunity against S. mutans and show that the orphan regulator CovR (CovRSm) modulates susceptibility to complement opsonization and survival in blood. S. mutans blood isolates showed reduced susceptibility to C3b deposition compared to oral isolates. Reduced expression of covRSm in blood strains was associated with increased transcription of CovRSm-repressed genes required for S. mutans interactions with glucans (gbpC, gbpB, and epsC), sucrose-derived exopolysaccharides (EPS). Consistently, blood strains showed an increased capacity to bind glucan in vitro. Deletion of covRSm in strain UA159 (UAcov) impaired C3b deposition and binding to serum IgG and C-reactive protein (CRP) as well as phagocytosis through C3b/iC3b receptors and killing by neutrophils. Opposite effects were observed in mutants of gbpC, epsC, or gtfBCD (required for glucan synthesis). C3b deposition on UA159 was abolished in C1q-depleted serum, implying that the classical pathway is essential for complement activation on S. mutans. Growth in sucrose-containing medium impaired the binding of C3b and IgG to UA159, UAcov, and blood isolates but had absent or reduced effects on C3b deposition in gtfBCD, gbpC, and epsC mutants. UAcov further showed increased ex vivo survival in human blood in an EPS-dependent way. Consistently, reduced survival was observed for the gbpC and epsC mutants. Finally, UAcov showed an increased ability to cause bacteremia in a rat model. These results reveal that CovRSm modulates systemic virulence by regulating functions affecting S. mutans susceptibility to complement opsonization. PMID:27572331

Potassium humate inhibits complement activation and the production of inflammatory cytokines in vitro

Energy Technology Data Exchange (ETDEWEB)

van Rensburg, C.E.J.; Naude, P.J. [University of Pretoria, Pretoria (South Africa)

2009-08-15

The effects of brown coal derived potassium humate on lymphocyte proliferation, cytokine production and complement activation were investigated in vitro. Potassium humate increased lymphocyte proliferation of phytohaemaglutinin A (PHA) and pokeweed mitogen (PWM) stimulated mononuclear lymphocytes (MNL) in vitro from concentrations of 20 to 80 {mu} g/ml, in a dose dependant manner. On the other hand potassium humate, at 40 {mu} g/ml, significantly inhibited the release of TNF-alpha, IL-1 beta, IL-6 and IL-10 by PHA stimulated MNL. Regarding complement activation it was found that potassium humate inhibits the activation of both the alternative and classical pathways without affecting the stability of the red blood cell membranes. These results indicate that the anti-inflammatory potential of potassium humate could be partially due to the inhibition of pro-inflammatory cytokines responsible for the initiation of these reactions as well as inhibition of complement activation. The increased lymphocyte proliferation observed, might be due to increased IL-2 production as previously been documented.

Prostaglandins and complement changes in some conditions related to inflammation. [Mice

Energy Technology Data Exchange (ETDEWEB)

Eisen, V.; Walker, D.I.; Binysh, S.G.; Tedder, R.S.

1977-01-01

Exposure to ionizing radiation produces several systemic and local reactions which could be mediated by prostaglandins. Prostaglandin levels were therefore studied in blood and tissues of mice which had been exposed to x-rays. Significant increases were found in spleens after 200 to 700 R, and in lungs after 600 to 700 R. These changes were most pronounced 4 to 7 days after irradiation. Ionizing radiation promptly and potently reduced the activity of prostaglandin dehydrogenase in the spleen, whereas prostaglandin synthesis was less affected. Evidence was obtained for the activation and consumption of haemolytic complement in serum in the course of heart-lung operations involving extracorporeal circulation. Activation involved primarily the classical pathway, and only slightly the alternate pathway.

The Scl1 protein of M6-type group A Streptococcus binds the human complement regulatory protein, factor H, and inhibits the alternative pathway of complement.

Science.gov (United States)

Caswell, Clayton C; Han, Runlin; Hovis, Kelley M; Ciborowski, Pawel; Keene, Douglas R; Marconi, Richard T; Lukomski, Slawomir

2008-02-01

Non-specific activation of the complement system is regulated by the plasma glycoprotein factor H (FH). Bacteria can avoid complement-mediated opsonization and phagocytosis through acquiring FH to the cell surface. Here, we characterize an interaction between the streptococcal collagen-like protein Scl1.6 of M6-type group A Streptococcus (GAS) and FH. Using affinity chromatography with immobilized recombinant Scl1.6 protein, we co-eluted human plasma proteins with molecular weight of 155 kDa, 43 kDa and 38 kDa. Mass spectrometry identified the 155 kDa band as FH and two other bands as isoforms of the FH-related protein-1. The identities of all three bands were confirmed by Western immunoblotting with specific antibodies. Structure-function relation studies determined that the globular domain of the Scl1.6 variant specifically binds FH while fused to collagenous tails of various lengths. This binding is not restricted to Scl1.6 as the phylogenetically linked Scl1.55 variant also binds FH. Functional analyses demonstrated the cofactor activity of the rScl1.6-bound FH for factor I-mediated cleavage of C3b. Finally, purified FH bound to the Scl1.6 protein present in the cell wall material obtained from M6-type GAS. In conclusion, we have identified a functional interaction between Scl1 and plasma FH, which may contribute to GAS evasion of complement-mediated opsonization and phagocytosis.

A novel approach for modeling deregulated electricity markets

Energy Technology Data Exchange (ETDEWEB)

Rubin, Ofir D., E-mail: rubino@agri.huji.ac.i [Department of Agricultural Economics and Management, Hebrew University of Jerusalem, P.O. Box 12, Rehovot 76100 (Israel); Babcock, Bruce A., E-mail: babcock@iastate.ed [Department of Economics, Iowa State University, 578F Heady Hall, Ames, IA 50011-1070 (United States); Center for Agricultural and Rural Development (CARD), Iowa State University, Ames, IA 50011-1070 (United States)

2011-05-15

The theoretical framework developed in this study allows development of a model of deregulated electricity markets that explains two familiar empirical findings; the existence of forward premiums and price-cost markups in the spot market. This is a significant contribution because electricity forward premiums have been previously explained exclusively by the assumptions of perfect competition and risk-averse behavior while spot markups are generally the outcome of a body of literature assuming oligopolistic competition. Our theoretical framework indicates that a certain premium for forward contracting is required for efficient allocation of generation capacity. However, due to the uniqueness of electricity and the design of deregulated electricity markets this premium might be substantially higher than its optimal level. - Research highlights: {yields} The state of knowledge regarding modeling electricity markets is incomplete. {yields} Electricity forward premiums are not necessarily driven by risk aversion. {yields} Efficiency in production requires a certain premium for forward contracting. {yields} It is likely that market premiums are substantially higher than their optimal level. {yields} Policy regulation should not seek to eliminate forward premium entirely.

A novel approach for modeling deregulated electricity markets

International Nuclear Information System (INIS)

Rubin, Ofir D.; Babcock, Bruce A.

2011-01-01

The theoretical framework developed in this study allows development of a model of deregulated electricity markets that explains two familiar empirical findings; the existence of forward premiums and price-cost markups in the spot market. This is a significant contribution because electricity forward premiums have been previously explained exclusively by the assumptions of perfect competition and risk-averse behavior while spot markups are generally the outcome of a body of literature assuming oligopolistic competition. Our theoretical framework indicates that a certain premium for forward contracting is required for efficient allocation of generation capacity. However, due to the uniqueness of electricity and the design of deregulated electricity markets this premium might be substantially higher than its optimal level. - Research highlights: → The state of knowledge regarding modeling electricity markets is incomplete. → Electricity forward premiums are not necessarily driven by risk aversion. → Efficiency in production requires a certain premium for forward contracting. → It is likely that market premiums are substantially higher than their optimal level. → Policy regulation should not seek to eliminate forward premium entirely.

Human antibodies fix complement to inhibit Plasmodium falciparum invasion of erythrocytes and are associated with protection against malaria.

Science.gov (United States)

Boyle, Michelle J; Reiling, Linda; Feng, Gaoqian; Langer, Christine; Osier, Faith H; Aspeling-Jones, Harvey; Cheng, Yik Sheng; Stubbs, Janine; Tetteh, Kevin K A; Conway, David J; McCarthy, James S; Muller, Ivo; Marsh, Kevin; Anders, Robin F; Beeson, James G

2015-03-17

Antibodies play major roles in immunity to malaria; however, a limited understanding of mechanisms mediating protection is a major barrier to vaccine development. We have demonstrated that acquired human anti-malarial antibodies promote complement deposition on the merozoite to mediate inhibition of erythrocyte invasion through C1q fixation and activation of the classical complement pathway. Antibody-mediated complement-dependent (Ab-C') inhibition was the predominant invasion-inhibitory activity of human antibodies; most antibodies were non-inhibitory without complement. Inhibitory activity was mediated predominately via C1q fixation, and merozoite surface proteins 1 and 2 were identified as major targets. Complement fixation by antibodies was very strongly associated with protection from both clinical malaria and high-density parasitemia in a prospective longitudinal study of children. Ab-C' inhibitory activity could be induced by human immunization with a candidate merozoite surface-protein vaccine. Our findings demonstrate that human anti-malarial antibodies have evolved to function by fixing complement for potent invasion-inhibitory activity and protective immunity. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

[Secure cupboards, an advantage for the medicine use pathway].

Science.gov (United States)

Leclercq, Amandine; Foqué, Carole

2016-05-01

At Valenciennes general hospital, for some patients, the medicine use pathway is made secure through the use of computer systems which ensure named-patient daily dispensing. Secure cupboards are a complement to this main pathway. Copyright © 2016. Publié par Elsevier Masson SAS.

Complement drives glucosylceramide accumulation and tissue inflammation in Gaucher disease.

Science.gov (United States)

Pandey, Manoj K; Burrow, Thomas A; Rani, Reena; Martin, Lisa J; Witte, David; Setchell, Kenneth D; Mckay, Mary A; Magnusen, Albert F; Zhang, Wujuan; Liou, Benjamin; Köhl, Jörg; Grabowski, Gregory A

2017-03-02

Gaucher disease is caused by mutations in GBA1, which encodes the lysosomal enzyme glucocerebrosidase (GCase). GBA1 mutations drive extensive accumulation of glucosylceramide (GC) in multiple innate and adaptive immune cells in the spleen, liver, lung and bone marrow, often leading to chronic inflammation. The mechanisms that connect excess GC to tissue inflammation remain unknown. Here we show that activation of complement C5a and C5a receptor 1 (C5aR1) controls GC accumulation and the inflammatory response in experimental and clinical Gaucher disease. Marked local and systemic complement activation occurred in GCase-deficient mice or after pharmacological inhibition of GCase and was associated with GC storage, tissue inflammation and proinflammatory cytokine production. Whereas all GCase-inhibited mice died within 4-5 weeks, mice deficient in both GCase and C5aR1, and wild-type mice in which GCase and C5aR were pharmacologically inhibited, were protected from these adverse effects and consequently survived. In mice and humans, GCase deficiency was associated with strong formation of complement-activating GC-specific IgG autoantibodies, leading to complement activation and C5a generation. Subsequent C5aR1 activation controlled UDP-glucose ceramide glucosyltransferase production, thereby tipping the balance between GC formation and degradation. Thus, extensive GC storage induces complement-activating IgG autoantibodies that drive a pathway of C5a generation and C5aR1 activation that fuels a cycle of cellular GC accumulation, innate and adaptive immune cell recruitment and activation in Gaucher disease. As enzyme replacement and substrate reduction therapies are expensive and still associated with inflammation, increased risk of cancer and Parkinson disease, targeting C5aR1 may serve as a treatment option for patients with Gaucher disease and, possibly, other lysosomal storage diseases.

Less Government is Good Government? Deregulation as an Undermining Principle of Financial Markets

Directory of Open Access Journals (Sweden)

Tim Engartner

2010-07-01

Full Text Available Since liberalization became the dominant global narrative the stock response to market shortcomings has been to “slim down” the state and deregulate. In most countries the slogan of “less government is good government” has become a constitutive feature of economic policy since the 1980s. Markets lie at the heart of every successful economy, and despite not necessarily working well on their own, the economic policy of deregulation has been one of the most persistent currents in the global economy. Based as it is on classical liberalism and – at least in its origins and leanings – neoclassical theory, deregulation aims to minimize the influence of the state. But in the context of the current financial and economic meltdown – the worst economic dislocation since the Great Crash of 1929-32 – “downsizing” the state causes growing turmoil. Global networking has made financial markets much more volatile and therefore much more susceptible to crisis.

Economic theory and the failure of electricity deregulation in Sweden

International Nuclear Information System (INIS)

Banks, F.E.

2004-01-01

The deregulation of electricity has failed in Sweden. Since the beginning of the deregulation 'experiment', the trend price of electricity has increased much faster than the consumer price index, especially during recent years. More importantly, because of (1) the lack of investment in domestic generating (and perhaps transmission) facilities by Swedish power companies, (2) the questionable strategy employed by these firms to mange hydroelectric reserves, (3) increased and to some extent irrational energy taxes, and (4) the beginning of nuclear 'disengagement', households and businesses are vulnerable to a prolonged 'spike' in electricity prices. Everything considered, the recent history of the Swedish electricity sector - and particularly that of the overpraised Nordic Electric Exchange (i.e. Nord Pool) - should be considered a wake-up call instead of an example. (author)

Deregulation potentials in the Federal Republic of Germany. Deregulierungspotentiale in der Bundesrepublik

Energy Technology Data Exchange (ETDEWEB)

Soltwedel, R; Busch, A; Gross, A; Laaser, C F

1986-01-01

In December 1984 the Federal Minister of Economics commissioned the Institute of World Trade and Industry to work out an expertise on 'deregulation potentials in the Federal Republic of Germany'. The study gives access to major parts of the expertise. Analyses focus on regulations for different self-supporting occupations, retail trade, the finance markets, the communication sector, the supply industry, and the transportation sector. An examination of the grounds the regulations were based on is followed by a discussion of the pros and cons of a deregulation. The statements and arguments take into account experiences gained abroad.

The End of a Natural Monopoly. Deregulation and Competition in the Electric Power Industry

International Nuclear Information System (INIS)

Grossman, P.Z.; Cole, D.H.

2003-01-01

For a hundred years, scholars and government officials understood, or thought they did, the electric power industry. Electric power, based on a single, large service provider, connected by wires to all of its customers, was thought to be an industry that could only operate efficiently as a monopoly; indeed it was something called a 'natural monopoly'. Since it had to be a monopoly, with all the attendant inefficiencies and potential market abuses monopoly entails, government regulation was necessary. These basic assumptions, which at times seemed to conflict with observed facts remained largely unquestioned for the better part of 75 years. Then, changing institutional and technological circumstances led economists to question the basis in fact of the theory of natural monopoly, and the regulatory system it entailed. Movement toward a deregulated electric power system began albeit in piece-meal fashion. Indeed, the result has been a crazy quilt of deregulation and re-regulations, which often have resulted in more costs than benefits for society as a whole. In the most infamous case, California, the entire enterprise of regulatory change has been called into question. The process of deregulation or reregulation in several other states has stopped because of fear of repeating California's mistakes. This book addresses some of the fundamental issues underlying the debate over electric power regulation and deregulation. Only by understanding these questions and exploring a variety of possible answers to them can we hope to move the debate over the proper structure of the electric power industry. Undoubtedly, electric power deregulation will be a major legal and economic concern for years to come

Insurance brokers market dynamics in Poland before deregulation

Directory of Open Access Journals (Sweden)

Jarosław Krajewski

2014-12-01

Full Text Available The article focus on insurance broker profession in connection with second part of professions deregulations. It briefly presents modifications in polish law in this domain. Next part concerns the insurance brokers market dynamics analysis. The results shows permanent increase in brokers quantity in spite of existing regulations. Presented paper makes start point to following analysis.

Growth strategies of electric utilities in context of deregulation and liberalization of electricity market

Directory of Open Access Journals (Sweden)

Maria Đogić

2017-01-01

Full Text Available This paper identifies the growth strategies adopted by the electric utilities sector in the context of changes resulting from the deregulation and liberalization of the electricity market. Strategies pursued by the electric utilities sector were rarely the subject of research in the field of strategic management despite the fact that electricity is an indispensable element of everyday life and the economy as a whole. Therefore, a case study of the largest incumbent electric utilities in the Republic of Croatia, Slovenia, Bosnia and Herzegovina, Serbia, Montenegro, and Macedonia has been conducted, and differences in the degree of market liberalization and core features of these companies have been noted. Research findings have shown that the degree of deregulation can affect the growth strategies of electric utilities. In those countries where the degree of deregulation is lower, electric utilities focus on the domestic market. On the other hand, a higher level of deregulation enables electric utilities to achieve their growth through diversification or innovation. Given the fact that the analyzed electric utilities are operating within relatively small economies, they cannot compete with electric utilities in developed countries, and, apart from international electricity trading, are mostly focused on their domestic markets.

Deregulation of E2-EPF ubiquitin carrier protein in papillary renal cell carcinoma.

Science.gov (United States)

Roos, Frederik C; Evans, Andrew J; Brenner, Walburgis; Wondergem, Bill; Klomp, Jeffery; Heir, Pardeep; Roche, Olga; Thomas, Christian; Schimmel, Heiko; Furge, Kyle A; Teh, Bin T; Thüroff, Joachim W; Hampel, Christian; Ohh, Michael

2011-02-01

Molecular pathways associated with pathogenesis of sporadic papillary renal cell carcinoma (PRCC), the second most common form of kidney cancer, are poorly understood. We analyzed primary tumor specimens from 35 PRCC patients treated by nephrectomy via gene expression analysis and tissue microarrays constructed from an additional 57 paraffin-embedded PRCC samples via immunohistochemistry. Gene products were validated and further studied by Western blot analyses using primary PRCC tumor samples and established renal cell carcinoma cell lines, and potential associations with pathologic variables and survival in 27 patients with follow-up information were determined. We show that the expression of E2-EPF ubiquitin carrier protein, which targets the principal negative regulator of hypoxia-inducible factor (HIF), von Hippel-Lindau protein, for proteasome-dependent degradation, is markedly elevated in the majority of PRCC tumors exhibiting increased HIF1α expression, and is associated with poor prognosis. In addition, we identified multiple hypoxia-responsive elements within the E2-EPF promoter, and for the first time we demonstrated that E2-EPF is a hypoxia-inducible gene directly regulated via HIF1. These findings reveal deregulation of the oxygen-sensing pathway impinging on the positive feedback mechanism of HIF1-mediated regulation of E2-EPF in PRCC. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Deregulation, privatization and the Ontario power failure

International Nuclear Information System (INIS)

2003-09-01

The Canadian Union of Public Employees (CUPE) has examined the history of deregulation of the electricity industry in the United States and presents lessons that could be learned from the California electricity crisis, the collapse of Enron, and the massive blackout that occurred in August 2003 across Ontario and northeastern United States. Unlike the United States, Canada's electricity system is mostly publicly owned and operated. This report emphasized that the need for public investment in the electricity system is greater than ever, and offers suggestions on how to strengthen the Canadian electricity system. It examines the attempts made to deregulate and privatize the electricity system in Ontario, Alberta, New Brunswick and British Columbia and exposes the reality of price caps and the debt of public utilities. It demonstrates that privatization has failed to provide a safe, reliable, affordable and adequate supply of electricity. The report claims that profit-seeking power producers want to keep supply and demand in their favour to sell electricity at the highest possible price. In addition to emphasizing the need for public investment in the electricity system, this report emphasizes the need for Canadian electricity cooperation, with particular mention of the large energy supplies in Manitoba and Quebec. 37 refs

Assessing the Significance of Telecommunication Deregulation on the Growth of Japan's Mobile Phone Market

OpenAIRE

Yuqing Xing

2001-01-01

This paper analyzes the development of Japan's mobile phone market. Specifically, it focuses on the regulatory reforms of Japan's mobile communication sector and their impact on the growth of the market. The analysis based on a monopolistic competition model shows that the deregulation policies perform an essential role in fostering the rapid expansion of Japan's mobile phone market. Using quarterly data from 1991 to 1999, the paper tests the significance of the telecommunication deregulation...

Gas prices deregulation: how to play the game well?

International Nuclear Information System (INIS)

Petitot, Pauline

2014-01-01

At the instigation of the European Union and in a context of increasing deregulation, the end of regulated gas prices in France is coming soon. Suppliers and consumers concerned are actively preparing themselves to take the turn of gas market liberalization. This short paper reveals their strategies

Mercury-induced hepatotoxicity in zebrafish: in vivo mechanistic insights from transcriptome analysis, phenotype anchoring and targeted gene expression validation

Directory of Open Access Journals (Sweden)

Mathavan Sinnakaruppan

2010-03-01

Full Text Available Abstract Background Mercury is a prominent environmental contaminant that causes detrimental effects to human health. Although the liver has been known to be a main target organ, there is limited information on in vivo molecular mechanism of mercury-induced toxicity in the liver. By using transcriptome analysis, phenotypic anchoring and validation of targeted gene expression in zebrafish, mercury-induced hepatotoxicity was investigated and a number of perturbed cellular processes were identified and compared with those captured in the in vitro human cell line studies. Results Hepato-transcriptome analysis of mercury-exposed zebrafish revealed that the earliest deregulated genes were associated with electron transport chain, mitochondrial fatty acid beta-oxidation, nuclear receptor signaling and apoptotic pathway, followed by complement system and proteasome pathway, and thereafter DNA damage, hypoxia, Wnt signaling, fatty acid synthesis, gluconeogenesis, cell cycle and motility. Comparative meta-analysis of microarray data between zebrafish liver and human HepG2 cells exposed to mercury identified some common toxicological effects of mercury-induced hepatotoxicity in both models. Histological analyses of liver from mercury-exposed fish revealed morphological changes of liver parenchyma, decreased nucleated cell count, increased lipid vesicles, glycogen and apoptotic bodies, thus providing phenotypic evidence for anchoring of the transcriptome analysis. Validation of targeted gene expression confirmed deregulated gene-pathways from enrichment analysis. Some of these genes responding to low concentrations of mercury may serve as toxicogenomic-based markers for detection and health risk assessment of environmental mercury contaminations. Conclusion Mercury-induced hepatotoxicity was triggered by oxidative stresses, intrinsic apoptotic pathway, deregulation of nuclear receptor and kinase activities including Gsk3 that deregulates Wnt signaling

Computer-Aided Targeting of the PI3K/Akt/mTOR Pathway: Toxicity Reduction and Therapeutic Opportunities

Directory of Open Access Journals (Sweden)

Tan Li

2014-10-01

Full Text Available The PI3K/Akt/mTOR pathway plays an essential role in a wide range of biological functions, including metabolism, macromolecular synthesis, cell growth, proliferation and survival. Its versatility, however, makes it a conspicuous target of many pathogens; and the consequential deregulations of this pathway often lead to complications, such as tumorigenesis, type 2 diabetes and cardiovascular diseases. Molecular targeted therapy, aimed at modulating the deregulated pathway, holds great promise for controlling these diseases, though side effects may be inevitable, given the ubiquity of the pathway in cell functions. Here, we review a variety of factors found to modulate the PI3K/Akt/mTOR pathway, including gene mutations, certain metabolites, inflammatory factors, chemical toxicants, drugs found to rectify the pathway, as well as viruses that hijack the pathway for their own synthetic purposes. Furthermore, this evidence of PI3K/Akt/mTOR pathway alteration and related pathogenesis has inspired the exploration of computer-aided targeting of this pathway to optimize therapeutic strategies. Herein, we discuss several possible options, using computer-aided targeting, to reduce the toxicity of molecularly-targeted therapy, including mathematical modeling, to reveal system-level control mechanisms and to confer a low-dosage combination therapy, the potential of PP2A as a therapeutic target, the formulation of parameters to identify patients who would most benefit from specific targeted therapies and molecular dynamics simulations and docking studies to discover drugs that are isoform specific or mutation selective so as to avoid undesired broad inhibitions. We hope this review will stimulate novel ideas for pharmaceutical discovery and deepen our understanding of curability and toxicity by targeting the PI3K/Akt/mTOR pathway.

Revenue opportunities for gas plants arising from electricity deregulation

International Nuclear Information System (INIS)

Bachmann, G.C.

1999-01-01

A brief overview of deregulation in the electric power industry and an explanation of how these changes can be used to increase revenues of gas processing plants is provided. Deregulation in the electric power industry provides the potential to significantly reduce energy costs for the gas plant and allows technology to be applied to make a better use of a valuable commodity. Owners and operators of gas processing plants increase their operating income by taking advantage of co-generation systems which provide heat and electrical energy to the gas plant. Such an application has three revenue streams, the main one being the power sales to the gas plant, the second one heat sales, and the third increased revenues from the gas plant through a reduction of overall costs, not to mention significantly reduced downtime. Further savings are possible through diversion of excess energy produced to other facilities owned by the gas plant owner

The impact of deregulation on the US nuclear industry

Energy Technology Data Exchange (ETDEWEB)

Baratta, A.J. [Pennsylvania State Univ., Nuclear Safety Center, University Park, PA (United States)

2001-07-01

In the United States, the electric utility industry is undergoing a dramatic shift away from a tightly regulated monopoly to a free market system. The impact on the nuclear utility industry of deregulation coupled with recent changes in the nuclear regulatory environment has had a dramatic impact on the future of nuclear power in the United States. Utilities have been broken up into separate generation, transmission, and distribution companies and are now allowed to sell electricity outside of their former service areas. As economic deregulation has occurred, the U.S. Nuclear Regulatory Commission has also adopted a new approach to regulation -- risk informed regulation. The implementation of risk-informed regulation has resulted in the adoption of a new regulatory format that attempts to highlight those areas having greatest risk significance. This paper explores these and other changes that have resulted because of the changing economic and regulatory environment for nuclear energy and examines their impact on the future of nuclear energy in the United States. (author)

The impact of deregulation on the US nuclear industry

International Nuclear Information System (INIS)

Baratta, A.J.

2001-01-01

In the United States, the electric utility industry is undergoing a dramatic shift away from a tightly regulated monopoly to a free market system. The impact on the nuclear utility industry of deregulation coupled with recent changes in the nuclear regulatory environment has had a dramatic impact on the future of nuclear power in the United States. Utilities have been broken up into separate generation, transmission, and distribution companies and are now allowed to sell electricity outside of their former service areas. As economic deregulation has occurred, the U.S. Nuclear Regulatory Commission has also adopted a new approach to regulation -- risk informed regulation. The implementation of risk-informed regulation has resulted in the adoption of a new regulatory format that attempts to highlight those areas having greatest risk significance. This paper explores these and other changes that have resulted because of the changing economic and regulatory environment for nuclear energy and examines their impact on the future of nuclear energy in the United States. (author)

Staphylococcus aureus SdrE captures complement factor H's C-terminus via a novel 'close, dock, lock and latch' mechanism for complement evasion.

Science.gov (United States)

Zhang, Yingjie; Wu, Minhao; Hang, Tianrong; Wang, Chengliang; Yang, Ye; Pan, Weimin; Zang, Jianye; Zhang, Min; Zhang, Xuan

2017-05-04

Complement factor H (CFH) is a soluble complement regulatory protein essential for the down-regulation of the alternative pathway on interaction with specific markers on the host cell surface. It recognizes the complement component 3b (C3b) and 3d (C3d) fragments in addition to self cell markers (i.e. glycosaminoglycans, sialic acid) to distinguish host cells that deserve protection from pathogens that should be eliminated. The Staphylococcus aureus surface protein serine-aspartate repeat protein E (SdrE) was previously reported to bind human CFH as an immune-evasion tactic. However, the molecular mechanism underlying SdrE-CFH-mediated immune evasion remains unknown. In the present study, we identified a novel region at CFH's C-terminus (CFH 1206-1226 ), which binds SdrE N2 and N3 domains (SdrE N2N3 ) with high affinity, and determined the crystal structures of apo-SdrE N2N3 and the SdrE N2N3 -CFH 1206-1226 complex. Comparison of the structure of the CFH-SdrE complex with other CFH structures reveals that CFH's C-terminal tail flips from the main body to insert into the ligand-binding groove of SdrE. In addition, SdrE N2N3 adopts a 'close' state in the absence of CFH, which undergoes a large conformational change on CFH binding, suggesting a novel 'close, dock, lock and latch' (CDLL) mechanism for SdrE to recognize its ligand. Our findings imply that SdrE functions as a 'clamp' to capture CFH's C-terminal tail via a unique CDLL mechanism and sequesters CFH on the surface of S. aureus for complement evasion. © 2017 The Author(s).

Power grab : the impacts of power market deregulation on B.C.'s environment and consumers

International Nuclear Information System (INIS)

Simmons, G.; Howard, T.; Christensen, R.

2002-07-01

The government of British Columbia is developing a new energy policy that will include the deregulation of the province's integrated, publicly-owned electric utilities. The BC Citizens for Public Power Society presents its views on the impact this will have on the BC environment and consumers. It argues that deregulation will result in increased pollution and environmental degradation from new coal and natural gas fired power plants. Deregulation will also result in a lack of accountability and control in the power maker, and prices will increase by a predicted minimum 30 per cent. In addition, the increased price and supply volatility will result in brownouts. This report also discussed the impact that deregulation would have on the transmission system. It was noted that if the public electricity resources are removed from public ownership and control, the province's future options will be restricted under the North American Free Trade Agreement (NAFTA) and the General Agreement on Trade in Services (GATS). The BC Citizens for Public Power Society argues that the future power needs of the province are best met by public investment and energy conservation using BC Hydro. 65 refs

Price-elastic demand in deregulated electricity markets

OpenAIRE

Siddiqui, Afzal S.

2003-01-01

The degree to which any deregulated market functions efficiently often depends on the ability of market agents to respond quickly to fluctuating conditions. Many restructured electricity markets, however, experience high prices caused by supply shortages and little demand-side response. We examine the implications for market operations when a risk-averse retailer's end-use consumers are allowed to perceive real-time variations in the electricity spot price. Using a market-equilibrium mo...

CSF coccidioides complement fixation

Science.gov (United States)

... this page: //medlineplus.gov/ency/article/003526.htm CSF coccidioides complement fixation test To use the sharing features on this page, please enable JavaScript. CSF coccidioides complement fixation is a test that checks ...

Immunological Deregulation in Classic Hodgkin Lymphoma

Science.gov (United States)

Romano, Alessandra; Vetro, Calogero; Caocci, Giovanni; Greco, Marianna; Parrinello, Nunziatina Laura; Di Raimondo, Francesco; La Nasa, Giorgio

2014-01-01

Classic Hodgkin Lymphoma (cHL) has a unique histology since only a few neoplastic cells are surrounded by inflammatory accessory cells that in the last years have emerged as crucial players in sustaining the course of disease. In addition, recent studies suggest that the abnormal activity of these inflammatory cells (such as deregulation in regulatory T cells signaling, expansion of myeloid derived suppressor cells, HLA-G signaling and natural killer cells dysfunction) may have prognostic significance. This review is focused on summarizing recent advanced in immunological defects in cHL with translational implications. PMID:24959336

Inhibition of the complement system by saliva of Anopheles (Nyssorhynchus) aquasalis.

Science.gov (United States)

Mendes-Sousa, Antonio Ferreira; Vale, Vladimir Fazito; Queiroz, Daniel Costa; Pereira-Filho, Adalberto Alves; da Silva, Naylene Carvalho Sales; Koerich, Leonardo Barbosa; Moreira, Luciano Andrade; Pereira, Marcos Horácio; Sant'Anna, Maurício Roberto; Araújo, Ricardo Nascimento; Andersen, John; Valenzuela, Jesus Gilberto; Gontijo, Nelder Figueiredo

2018-01-01

Anopheline mosquitoes are vectors of malaria parasites. Their saliva contains anti-hemostatic and immune-modulator molecules that favor blood feeding and parasite transmission. In this study, we describe the inhibition of the alternative pathway of the complement system (AP) by Anopheles aquasalis salivary gland extracts (SGE). According to our results, the inhibitor present in SGE acts on the initial step of the AP blocking deposition of C3b on the activation surfaces. Properdin, which is a positive regulatory molecule of the AP, binds to SGE. When SGE was treated with an excess of properdin, it was unable to inhibit the AP. Through SDS-PAGE analysis, A. aquasalis presented a salivary protein with the same molecular weight as recombinant complement inhibitors belonging to the SG7 family described in the saliva of other anopheline species. At least some SG7 proteins bind to properdin and are AP inhibitors. Searching for SG7 proteins in the A. aquasalis genome, we retrieved a salivary protein that shared an 85% identity with albicin, which is the salivary alternative pathway inhibitor from A. albimanus. This A. aquasalis sequence was also very similar (81% ID) to the SG7 protein from A. darlingi, which is also an AP inhibitor. Our results suggest that the salivary complement inhibitor from A. aquasalis is an SG7 protein that can inhibit the AP by binding to properdin and abrogating its stabilizing activity. Albicin, which is the SG7 from A. albimanus, can directly inhibit AP convertase. Given the high similarity of SG7 proteins, the SG7 from A. aquasalis may also directly inhibit AP convertase in the absence of properdin. Copyright © 2017 Elsevier Ltd. All rights reserved.

Deregulation from the gas utility`s perspective [In New Zealand

Energy Technology Data Exchange (ETDEWEB)

Hammond, A.E. [Gas Association, Wellington (New Zealand)

1995-09-01

The paper covers the process of energy sector reform as it relates to the New Zealand Gas Industry. The reform processes are aimed at deregulating the gas industry, encouraging competition within the energy sector, and providing only light-handed controls in the areas of transmission and distribution where competition is unlikely. The paper concentrates on the technical aspects and views the process from the utility point of view. The first section looks at the specific elements of the energy sector reform legislation and identifies the changes that were brought about through the new Gas Act, the Gas Regulations and associated law amendments. The changes range from the removal of the exclusive franchises and price control through to the development of a new regime to control gasfitting and gas appliances. The second section reviews the relevant aspects of the broader changes of the deregulation process which have impacted on all New Zealand industries as the country moves through the 90s. These changes range from new legislation to manage resources through to changes in the health and safety area. The final section covers the activities and initiatives of the Gas Industry to optimise the opportunities that the deregulation process provides. These changes range from the preparation of access agreements for transportation of gas through to new training structures to ensure that adequate skills are available to maintain the industry`s excellent safety and reliability round. (Author)

Cycles in deregulated electricity markets: Empirical evidence from two decades

International Nuclear Information System (INIS)

Arango, Santiago; Larsen, Erik

2011-01-01

In this article, we discuss the 'cycle hypothesis' in electricity generation, which states that the introduction of deregulation in an electricity system might lead to sustained fluctuations of over- and under-capacity. The occurrence of cycles is one of the major threats for electricity markets as it affects the security of supply, and creates uncertainty in both the profitability of electricity companies and in consumer prices. We discuss the background for these cycles using analogies with other capital-intensive industries, along with evidence from the analysis of behavioral simulation models as well as from experimental electricity markets. Using data from the oldest deregulated markets we find support for the hypothesis in the case of the English and Chilean markets, based on an autocorrelation analysis. Evidence from the Nordpool market is more ambiguous, although we might be observing the first half of a cycle in generation capacity. Comparing a simulation of the English market performed in 1992 with the actual performance we can observe that the qualitative behavior of the model is consistent with the actual evolution. Finally, we discuss possible mechanisms for damping cycles in electricity generation, such as mothballing, capacity payments, and reliability markets. - Research highlights: → We explore the emergence of cycles in the electricity generation capacity after deregulation. → We discuss the reason for cycles in generation capacity and compare different theories. → Analysis of England and Chile data show strong indications that cycles have emerged.

Structural Reforms and Growth : Product and Labor Market Deregulations

NARCIS (Netherlands)

Eijffinger, S.C.W.; Rossi, A.

2006-01-01

The paper focuses on labor and product market deregulations, as fundamental elements in the passage from an investment to an innovation-based economy.The approach undertaken is prominently empirical.After a very brief description of the regulatory levels on the two sides of the Atlantic, we take two

Controlling the complement system in inflammation.

Science.gov (United States)

Kirschfink, M

1997-12-01

Inappropriate or excessive activation of the complement system can lead to harmful, potentially life-threatening consequences due to severe inflammatory tissue destruction. These consequences are clinically manifested in various disorders, including septic shock, multiple organ failure and hyperacute graft rejection. Genetic complement deficiencies or complement depletion have been proven to be beneficial in reducing tissue injury in a number of animal models of severe complement-dependent inflammation. It is therefore believed that therapeutic inhibition of complement is likely to arrest the process of certain diseases. Attempts to efficiently inhibit complement include the application of endogenous soluble complement inhibitors (C1-inhibitor, recombinant soluble complement receptor 1- rsCR1), the administration of antibodies, either blocking key proteins of the cascade reaction (e.g. C3, C5), neutralizing the action of the complement-derived anaphylatoxin C5a, or interfering with complement receptor 3 (CR3, CD18/11b)-mediated adhesion of inflammatory cells to the vascular endothelium. In addition, incorporation of membrane-bound complement regulators (DAF-CD55, MCP-CD46, CD59) has become possible by transfection of the correspondent cDNA into xenogeneic cells. Thereby, protection against complement-mediated inflammatory tissue damage could be achieved in various animal models of sepsis, myocardial as well as intestinal ischemia/reperfusion injury, adult respiratory distress syndrome, nephritis and graft rejection. Supported by results from first clinical trials, complement inhibition appears to be a suitable therapeutic approach to control inflammation. Current strategies to specifically inhibit complement in inflammation have been discussed at a recent meeting on the 'Immune Consequences of Trauma, Shock and Sepsis', held from March 4-8, 1997, in Munich, Germany. The Congress (chairman: E. Faist, Munich, Germany), which was held in close cooperation with various

Nanomedicine and the complement paradigm.

Science.gov (United States)

Moghimi, S Moein; Farhangrazi, Z Shadi

2013-05-01

The role of complement in idiosyncratic reactions to nanopharmaceutical infusion is receiving increasing attention. We discuss this in relation to nanopharmaceutical development and the possible use of complement inhibitors to prevent related adverse reactions. We further call on initiation of genetic association studies to unravel the genetic basis of nanomedicine infusion-related adverse responses, since most of the polymorphic genes in the genome belong to the immune system. In this paper, idiosyncratic reactions based on complement activation are discussed in the context of newly available complement inhibitors. Copyright © 2013 Elsevier Inc. All rights reserved.

Mesenchymal stromal cells engage complement and complement receptor bearing innate effector cells to modulate immune responses.

Directory of Open Access Journals (Sweden)

Guido Moll

Full Text Available Infusion of human third-party mesenchymal stromal cells (MSCs appears to be a promising therapy for acute graft-versus-host disease (aGvHD. To date, little is known about how MSCs interact with the body's innate immune system after clinical infusion. This study shows, that exposure of MSCs to blood type ABO-matched human blood activates the complement system, which triggers complement-mediated lymphoid and myeloid effector cell activation in blood. We found deposition of complement component C3-derived fragments iC3b and C3dg on MSCs and fluid-phase generation of the chemotactic anaphylatoxins C3a and C5a. MSCs bound low amounts of immunoglobulins and lacked expression of complement regulatory proteins MCP (CD46 and DAF (CD55, but were protected from complement lysis via expression of protectin (CD59. Cell-surface-opsonization and anaphylatoxin-formation triggered complement receptor 3 (CD11b/CD18-mediated effector cell activation in blood. The complement-activating properties of individual MSCs were furthermore correlated with their potency to inhibit PBMC-proliferation in vitro, and both effector cell activation and the immunosuppressive effect could be blocked either by using complement inhibitor Compstatin or by depletion of CD14/CD11b-high myeloid effector cells from mixed lymphocyte reactions. Our study demonstrates for the first time a major role of the complement system in governing the immunomodulatory activity of MSCs and elucidates how complement activation mediates the interaction with other immune cells.

Complement 5a stimulates macrophage polarization and contributes to tumor metastases of colon cancer.

Science.gov (United States)

Piao, Chunmei; Zhang, Wen-Mei; Li, Tao-Tao; Zhang, Cong-Cong; Qiu, Shulan; Liu, Yan; Liu, Sa; Jin, Ming; Jia, Li-Xin; Song, Wen-Chao; Du, Jie

2018-05-15

Inflammatory cells such as macrophages can play a pro-tumorigenic role in the tumor stroma. Tumor-associated macrophages (TAMs) generally display an M2 phenotype with tumor-promoting activity; however, the mechanisms regulating the TAM phenotype remain unclear. Complement 5a (C5a) is a cytokine-like polypeptide that is generated during complement system activation and is known to promote tumor growth. Herein, we investigated the role of C5a on macrophage polarization in colon cancer metastasis in mice. We found that deficiency of the C5a receptor (C5aR) severely impairs the metastatic ability of implanted colon cancer cells. C5aR was expressed on TAMs, which exhibited an M2-like functional profile in colon cancer liver metastatic lesions. Furthermore, C5a mediated macrophage polarization and this process relied substantially on activation of the nuclear factor-kappa B (NF-κB) pathway. Finally, analysis of human colon carcinoma indicated that C5aR expression is negatively associated with tumor differentiation grade. Our results demonstrate that C5aR has a central role in regulating the M2 phenotype of TAMs, which in turn, contributes to hepatic metastasis of colon cancer through NF-κB signaling. C5a is a potential novel marker for cancer prognosis and drugs targeting complement system activation, specifically the C5aR pathway, may offer new therapeutic opportunities for colon cancer management. Copyright © 2018 Elsevier Inc. All rights reserved.

Conference Proceedings: Effectively utilizing energy derivatives in a deregulated electricity market

International Nuclear Information System (INIS)

1998-01-01

This conference was devoted to a discussion about the likely impacts of deregulation on electricity markets in North America. Many of the presentations emphasized price risk in a competitive open access energy market. It was noted that deregulation is frequently associated with the creation of larger companies, higher risks and lower costs. Some of the individual topics addressed by the speakers included discussion of : (1) how underlying physical markets will work in Ontario, (2) experiences in derivative trading in the natural gas industry, (3) how to create value through multiple commodity risk management products, (4) trading with energy derivatives in the U.S. (5) how derivatives can add value for municipal electrical utilities, and (6) risk management mechanisms for energy derivative trading. refs., tabs., figs

HPV: Molecular pathways and targets.

Science.gov (United States)

Gupta, Shilpi; Kumar, Prabhat; Das, Bhudev C

2018-04-05

Infection of high-risk human papillomaviruses (HPVs) is a prerequisite for the development of cervical carcinoma. HPV infections are also implicated in the development of other types of carcinomas. Chronic or persistent infection of HPV is essential but HPV alone is inadequate, additional endogenous or exogenous cues are needed along with HPV to induce cervical carcinogenesis. The strategies that high-risk HPVs have developed in differentiating epithelial cells to reach a DNA-synthesis competent state leading to tumorigenic transformation are basically due to overexpression of the E6 and E7 oncoproteins and the activation of diverse cellular regulatory or signaling pathways that are targeted by them. Moreover, the Wnt/β-catenin/Notch and phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathways are deregulated in various cancers, and have also been implicated in HPV-induced cancers. These are basically related to the "cancer hallmarks," and include sustaining proliferative signals, the evasion of growth suppression and immune destruction, replicative immortality, inflammation, invasion, metastasis and angiogenesis, as well as genome instability, resisting cell death, and deregulation of cellular energetics. These information could eventually aid in identifying or developing new diagnostic, prognostic biomarkers, and may contribute to design more effective targeted therapeutics and treatment strategies. Although surgery, chemotherapy and radiotherapy can cure more than 90% of women with early stage cervical cancer, the recurrent and metastatic disease remains a major cause of cancer mortality. Numerous efforts have been made to design new drugs and develop gene therapies to treat cervical cancer. In recent years, research on treatment strategies has proposed several options, including the role of HPV E5, E6, and E7 oncogenes, which are retained and overexpressed in most of the cervical cancers and whose respective oncoproteins are critical to the induction

An Agent-based Application to Enable Deregulated Energy Markets

NARCIS (Netherlands)

Capodieci, Nicola; Cabri, Giacomo; Pagani, Giuliano Andrea; Aiello, Marco

2012-01-01

Private houses are more and more enabled with devices that can produce renewable energy, and the not so remote chance of selling the surplus energy makes them new players in the energy market. This market is likely to become deregulated since each energy home-producer can negotiate the energy price

Structural and functional characterization of human complement factor P

DEFF Research Database (Denmark)

Pedersen, Dennis

not yet been resolved. This PhD-thesis provide structural understanding of the FP mediated stabilization of the AP C3 convertase. Furthermore, functional studies involving oligomeric and monomeric FP variants have helped us to understand the importance of FP oligomerization for the primary functions of FP...... of complement by stabilizing the C3 convertase complex (C3bBb). FP has also been suggested to serve as a pattern recognition molecule for the initiation of the alternative pathway. However, the molecular mechanisms of FP remain unclear due to its oligomeric nature and hence the atomic structure of FP has...

Block of the Mevalonate Pathway Triggers Oxidative and Inflammatory Molecular Mechanisms Modulated by Exogenous Isoprenoid Compounds

Directory of Open Access Journals (Sweden)

Paola Maura Tricarico

2014-04-01

Full Text Available Deregulation of the mevalonate pathway is known to be involved in a number of diseases that exhibit a systemic inflammatory phenotype and often neurological involvements, as seen in patients suffering from a rare disease called mevalonate kinase deficiency (MKD. One of the molecular mechanisms underlying this pathology could depend on the shortage of isoprenoid compounds and the subsequent mitochondrial damage, leading to oxidative stress and pro-inflammatory cytokines’ release. Moreover, it has been demonstrated that cellular death results from the balance between apoptosis and pyroptosis, both driven by mitochondrial damage and the molecular platform inflammasome. In order to rescue the deregulated pathway and decrease inflammatory markers, exogenous isoprenoid compounds were administered to a biochemical model of MKD obtained treating a murine monocytic cell line with a compound able to block the mevalonate pathway, plus an inflammatory stimulus. Our results show that isoprenoids acted in different ways, mainly increasing the expression of the evaluated markers [apoptosis, mitochondrial dysfunction, nucleotide-binding oligomerization-domain protein-like receptors 3 (NALP3, cytokines and nitric oxide (NO]. Our findings confirm the hypothesis that inflammation is triggered, at least partially, by the shortage of isoprenoids. Moreover, although further studies are necessary, the achieved results suggest a possible role for exogenous isoprenoids in the treatment of MKD.

The limits to deregulation of entry and expansion of the US gas pipeline industry

International Nuclear Information System (INIS)

Rosput, P.G.

1993-01-01

US consumers of natural gas have enjoyed significant benefits as the pricing of the commodity has been deregulated. Thanks in large part to the success of deregulation of the natural gas commodity. US federal regulators have embarked upon a wide-ranging programme of eliminating barriers to entry and expansion of natural gas pipelines, which have traditionally been regulated as natural monopolies. As a result, there is now significant excess capacity in the natural gas transmission sector, without measurable benefits to consumers. (author)

Staphylococcus aureus SdrE captures complement factor H's C-terminus via a novel ‘close, dock, lock and latch' mechanism for complement evasion

Science.gov (United States)

Zhang, Yingjie; Wu, Minhao; Hang, Tianrong; Wang, Chengliang; Yang, Ye; Pan, Weimin; Zang, Jianye

2017-01-01

Complement factor H (CFH) is a soluble complement regulatory protein essential for the down-regulation of the alternative pathway on interaction with specific markers on the host cell surface. It recognizes the complement component 3b (C3b) and 3d (C3d) fragments in addition to self cell markers (i.e. glycosaminoglycans, sialic acid) to distinguish host cells that deserve protection from pathogens that should be eliminated. The Staphylococcus aureus surface protein serine–aspartate repeat protein E (SdrE) was previously reported to bind human CFH as an immune-evasion tactic. However, the molecular mechanism underlying SdrE–CFH-mediated immune evasion remains unknown. In the present study, we identified a novel region at CFH's C-terminus (CFH1206–1226), which binds SdrE N2 and N3 domains (SdrEN2N3) with high affinity, and determined the crystal structures of apo-SdrEN2N3 and the SdrEN2N3–CFH1206–1226 complex. Comparison of the structure of the CFH–SdrE complex with other CFH structures reveals that CFH's C-terminal tail flips from the main body to insert into the ligand-binding groove of SdrE. In addition, SdrEN2N3 adopts a ‘close’ state in the absence of CFH, which undergoes a large conformational change on CFH binding, suggesting a novel ‘close, dock, lock and latch' (CDLL) mechanism for SdrE to recognize its ligand. Our findings imply that SdrE functions as a ‘clamp' to capture CFH's C-terminal tail via a unique CDLL mechanism and sequesters CFH on the surface of S. aureus for complement evasion. PMID:28258151

Deregulation in an energy market and its impact on R and D for low-carbon energy technology

International Nuclear Information System (INIS)

Nakada, Minoru

2005-01-01

This paper analyzes the impact of deregulation in an energy market on R and D activities for new energy technology when climate policy is implemented. A model of growth with vertical innovation is modified by including an oligopolistic energy supply sector for demonstrating to what extent deregulation in the energy supply sector will affect R and D activities for low-carbon energy technology, provided that carbon taxation is implemented. The analysis shows that, when the elasticity of substitution between input factors is less than unity, deregulation will drive energy R and D activities and reduce CO 2 accumulation if the energy market is highly concentrated in the beginning. (author)

Complement fixation test to C burnetii

Science.gov (United States)

... complement fixation test; Coxiella burnetii - complement fixation test; C burnetii - complement fixation test ... a specific foreign substance ( antigen ), in this case, C burnetii . Antibodies defend the body against bacteria, viruses, ...

Subversion of complement by hematophagous parasites.

Science.gov (United States)

Schroeder, Hélène; Skelly, Patrick J; Zipfel, Peter F; Losson, Bertrand; Vanderplasschen, Alain

2009-01-01

The complement system is a crucial part of innate and adaptive immunity which exerts a significant evolutionary pressure on pathogens. It has selected for those pathogens, mainly microorganisms but also parasites, that have evolved countermeasures. The characterization of how pathogens evade complement attack is a rapidly developing field of current research. In recent years, multiple complement evasion strategies have been characterized. In this review, we focus on complement escape mechanisms expressed by hematophagous parasites, a heterogeneous group of metazoan parasites that share the property of ingesting the whole blood of their host. Complement inhibition is crucial for parasite survival within the host tissue or to facilitate blood feeding. Finally, complement inhibition by hematophagous parasites may also contribute to their success as pathogen vectors.

Integrative Genomics Reveals Mechanisms of Copy Number Alterations Responsible for Transcriptional Deregulation in Colorectal Cancer

Science.gov (United States)

Camps, Jordi; Nguyen, Quang Tri; Padilla-Nash, Hesed M.; Knutsen, Turid; McNeil, Nicole E.; Wangsa, Danny; Hummon, Amanda B.; Grade, Marian; Ried, Thomas; Difilippantonio, Michael J.

2016-01-01

To evaluate the mechanisms and consequences of chromosomal aberrations in colorectal cancer (CRC), we used a combination of spectral karyotyping, array comparative genomic hybridization (aCGH), and array-based global gene expression profiling on 31 primary carcinomas and 15 established cell lines. Importantly, aCGH showed that the genomic profiles of primary tumors are recapitulated in the cell lines. We revealed a preponderance of chromosome breakpoints at sites of copy number variants (CNVs) in the CRC cell lines, a novel mechanism of DNA breakage in cancer. The integration of gene expression and aCGH led to the identification of 157 genes localized within high-level copy number changes whose transcriptional deregulation was significantly affected across all of the samples, thereby suggesting that these genes play a functional role in CRC. Genomic amplification at 8q24 was the most recurrent event and led to the overexpression of MYC and FAM84B. Copy number dependent gene expression resulted in deregulation of known cancer genes such as APC, FGFR2, and ERBB2. The identification of only 36 genes whose localization near a breakpoint could account for their observed deregulated expression demonstrates that the major mechanism for transcriptional deregulation in CRC is genomic copy number changes resulting from chromosomal aberrations. PMID:19691111

Increased Autoreactivity of the Complement-Activating Molecule Mannan-Binding Lectin in a Type 1 Diabetes Model

Directory of Open Access Journals (Sweden)

Jakob Appel Østergaard

2016-01-01

Full Text Available Background. Diabetic kidney disease is the leading cause of end-stage renal failure despite intensive treatment of modifiable risk factors. Identification of new drug targets is therefore of paramount importance. The complement system is emerging as a potential new target. The lectin pathway of the complement system, initiated by the carbohydrate-recognition molecule mannan-binding lectin (MBL, is linked to poor kidney prognosis in diabetes. We hypothesized that MBL activates complement upon binding within the diabetic glomerulus. Methods. We investigated this by comparing complement deposition and activation in kidneys from streptozotocin-induced diabetic mice and healthy control mice. Results. After 20 weeks of diabetes, glomerular deposition of MBL was significantly increased. Diabetic animals had 2.0-fold higher (95% CI 1.6–2.5 immunofluorescence intensity from anti-MBL antibodies compared with controls (P<0.001. Diabetes and control groups did not differ in glomerular immunofluorescence intensity obtained by antibodies against complement factors C4, C3, and C9. However, the circulating complement activation product C3a was increased in diabetes as compared to control mice (P=0.04. Conclusion. 20 weeks of diabetes increased MBL autoreactivity in the kidney and circulating C3a concentration. Together with previous findings, these results indicate direct effects of MBL within the kidney in diabetes.

Noun complement clauses as referential modifiers

Directory of Open Access Journals (Sweden)

Carlos de Cuba

2017-01-01

Full Text Available A number of recent analyses propose that so-called noun complement clauses should be analyzed as a type of relative clause. In this paper, I present a number of complications for any analysis that equates noun complement clauses to relative clauses, and conclude that this type of analysis is on the wrong track. I present cross-linguistic evidence showing that the syntactic behavior of noun complement clauses does not pattern with relative clauses. Patterns of complementizer choice and complementizer drop as well as patterns involving main clause phenomena and extraction differ in the two constructions, which I argue is unexpected under a relative clause analysis that involves operator movement. Instead I present an alternative analysis in which I propose that the referentiality of a noun complement clause is linked to its syntactic behavior. Following recent work, I claim that referential clauses have a syntactically truncated left-periphery, and this truncation can account for the lack of main clause phenomena in noun complement clauses. I argue that the truncation analysis is also able to accommodate complementizer data patterns more easily than relative clause analyses that appeal to operator movement.

Is further deregulation of the natural gas industry beneficial : discussion paper

Energy Technology Data Exchange (ETDEWEB)

Hoey, P.J. [Anbrer Consulting, Ottawa, ON (Canada)

2004-11-01

Energy market liberalization is a world trend that has prompted the deregulation of natural gas and electricity over the past twenty years in North America. The Ontario Energy Board and the National Energy Board are conducting public hearings on natural gas regulation in response to the request by Canadian energy industries for better regulatory streamlining. The following 5 issues regarding natural gas regulation in Canada have been examined: (1) system gas in a regulated market, (2) natural gas infrastructure investments and capital renewal, (3) improving efficiency in gas regulation, (4) expectations of performance-based regulation (PBR) in the natural gas industry, and (5) the debate whether further deregulation of the natural gas industry is beneficial. This paper examines if a competitive market exists in natural gas distribution and discusses the opportunities for further deregulation of the distribution and storage aspects of the industry. It was noted that the regulatory regime in Ontario will depend on how the Ontario Energy Board deals with issues regarding natural gas storage services. This paper also examines if new storage facilities can charge cost-based or market-based prices as well as the appropriate rate of return on capital to be used to determine those rates. It also examines what the requirement for non-discriminatory access to and from new storage facilities to the Dawn Hub and access to transmission capacity on Union Gas's Dawn to Trafalger pipeline system. Alternative fuels, franchises, bypasses, gated communities, distributed generation, market power and policy issues are the main factors that are considered in assessing the competition in natural gas distribution. It was concluded that further deregulation of the natural gas distribution system in Ontario is not warranted since there is not much possibility in developing a competitive market for distribution services in the short-term. However, the development of storage facilities

Is further deregulation of the natural gas industry beneficial : discussion paper

International Nuclear Information System (INIS)

Hoey, P.J.

2004-11-01

Energy market liberalization is a world trend that has prompted the deregulation of natural gas and electricity over the past twenty years in North America. The Ontario Energy Board and the National Energy Board are conducting public hearings on natural gas regulation in response to the request by Canadian energy industries for better regulatory streamlining. The following 5 issues regarding natural gas regulation in Canada have been examined: (1) system gas in a regulated market, (2) natural gas infrastructure investments and capital renewal, (3) improving efficiency in gas regulation, (4) expectations of performance-based regulation (PBR) in the natural gas industry, and (5) the debate whether further deregulation of the natural gas industry is beneficial. This paper examines if a competitive market exists in natural gas distribution and discusses the opportunities for further deregulation of the distribution and storage aspects of the industry. It was noted that the regulatory regime in Ontario will depend on how the Ontario Energy Board deals with issues regarding natural gas storage services. This paper also examines if new storage facilities can charge cost-based or market-based prices as well as the appropriate rate of return on capital to be used to determine those rates. It also examines what the requirement for non-discriminatory access to and from new storage facilities to the Dawn Hub and access to transmission capacity on Union Gas's Dawn to Trafalger pipeline system. Alternative fuels, franchises, bypasses, gated communities, distributed generation, market power and policy issues are the main factors that are considered in assessing the competition in natural gas distribution. It was concluded that further deregulation of the natural gas distribution system in Ontario is not warranted since there is not much possibility in developing a competitive market for distribution services in the short-term. However, the development of storage facilities in

Deregulated gas in 1985 seen costly

Energy Technology Data Exchange (ETDEWEB)

Schaffer, P.

1980-05-05

Deregulation of natural gas wellhead prices will mean higher prices for nonboiler industrial users, according to an Energy and Environmental Analysis Inc. (EEA) study. The price increases of high-sulfur residual fuel oil will exceed inflation rates, but low-sulfur residual oil and distillate oil will have smaller increases because of upgraded refineries. Te economc imact analysis is broken down by region and includes estimates of gas, high-sulfur coal, and low-sulfur coal prices thrugh 1995. Free copies of the report are available from the Federal Energy Regulatory Commission's Office of Public Information. (DCK)

The Sand Fly Salivary Protein Lufaxin Inhibits the Early Steps of the Alternative Pathway of Complement by Direct Binding to the Proconvertase C3b-B

Directory of Open Access Journals (Sweden)

Antonio F. Mendes-Sousa

2017-08-01

Full Text Available Saliva of the blood feeding sand fly Lutzomyia longipalpis was previously shown to inhibit the alternative pathway (AP of the complement system. Here, we have identified Lufaxin, a protein component in saliva, as the inhibitor of the AP. Lufaxin inhibited the deposition of C3b, Bb, Properdin, C5b, and C9b on agarose-coated plates in a dose-dependent manner. It also inhibited the activation of factor B in normal serum, but had no effect on the components of the membrane attack complex. Surface plasmon resonance (SPR experiments demonstrated that Lufaxin stabilizes the C3b-B proconvertase complex when passed over a C3b surface in combination with factor B. Lufaxin was also shown to inhibit the activation of factor B by factor D in a reconstituted C3b-B, but did not inhibit the activation of C3 by reconstituted C3b-Bb. Proconvertase stabilization does not require the presence of divalent cations, but addition of Ni2+ increases the stability of complexes formed on SPR surfaces. Stabilization of the C3b-B complex to prevent C3 convertase formation (C3b-Bb formation is a novel mechanism that differs from previously described strategies used by other organisms to inhibit the AP of the host complement system.

The Sand Fly Salivary Protein Lufaxin Inhibits the Early Steps of the Alternative Pathway of Complement by Direct Binding to the Proconvertase C3b-B.

Science.gov (United States)

Mendes-Sousa, Antonio F; do Vale, Vladimir Fazito; Silva, Naylene C S; Guimaraes-Costa, Anderson B; Pereira, Marcos H; Sant'Anna, Mauricio R V; Oliveira, Fabiano; Kamhawi, Shaden; Ribeiro, José M C; Andersen, John F; Valenzuela, Jesus G; Araujo, Ricardo N

2017-01-01

Saliva of the blood feeding sand fly Lutzomyia longipalpis was previously shown to inhibit the alternative pathway (AP) of the complement system. Here, we have identified Lufaxin, a protein component in saliva, as the inhibitor of the AP. Lufaxin inhibited the deposition of C3b, Bb, Properdin, C5b, and C9b on agarose-coated plates in a dose-dependent manner. It also inhibited the activation of factor B in normal serum, but had no effect on the components of the membrane attack complex. Surface plasmon resonance (SPR) experiments demonstrated that Lufaxin stabilizes the C3b-B proconvertase complex when passed over a C3b surface in combination with factor B. Lufaxin was also shown to inhibit the activation of factor B by factor D in a reconstituted C3b-B, but did not inhibit the activation of C3 by reconstituted C3b-Bb. Proconvertase stabilization does not require the presence of divalent cations, but addition of Ni 2+ increases the stability of complexes formed on SPR surfaces. Stabilization of the C3b-B complex to prevent C3 convertase formation (C3b-Bb formation) is a novel mechanism that differs from previously described strategies used by other organisms to inhibit the AP of the host complement system.

The Sand Fly Salivary Protein Lufaxin Inhibits the Early Steps of the Alternative Pathway of Complement by Direct Binding to the Proconvertase C3b-B

Science.gov (United States)

Mendes-Sousa, Antonio F.; do Vale, Vladimir Fazito; Silva, Naylene C. S.; Guimaraes-Costa, Anderson B.; Pereira, Marcos H.; Sant’Anna, Mauricio R. V.; Oliveira, Fabiano; Kamhawi, Shaden; Ribeiro, José M. C.; Andersen, John F.; Valenzuela, Jesus G.; Araujo, Ricardo N.

2017-01-01

Saliva of the blood feeding sand fly Lutzomyia longipalpis was previously shown to inhibit the alternative pathway (AP) of the complement system. Here, we have identified Lufaxin, a protein component in saliva, as the inhibitor of the AP. Lufaxin inhibited the deposition of C3b, Bb, Properdin, C5b, and C9b on agarose-coated plates in a dose-dependent manner. It also inhibited the activation of factor B in normal serum, but had no effect on the components of the membrane attack complex. Surface plasmon resonance (SPR) experiments demonstrated that Lufaxin stabilizes the C3b-B proconvertase complex when passed over a C3b surface in combination with factor B. Lufaxin was also shown to inhibit the activation of factor B by factor D in a reconstituted C3b-B, but did not inhibit the activation of C3 by reconstituted C3b-Bb. Proconvertase stabilization does not require the presence of divalent cations, but addition of Ni2+ increases the stability of complexes formed on SPR surfaces. Stabilization of the C3b-B complex to prevent C3 convertase formation (C3b-Bb formation) is a novel mechanism that differs from previously described strategies used by other organisms to inhibit the AP of the host complement system. PMID:28912782

Generation capacity adequacy in deregulated markets : options for Alberta

International Nuclear Information System (INIS)

Ayres, M.

2004-01-01

The Canadian Energy Research Institute (CERI) is a Calgary-based non-profit organization that conducts studies on energy and related environmental issues to help Canadian business and government organizations. This paper summarized the information in a two volume CERI study report which assessed generation capacity issues in deregulated electricity markets in Canada. The study observed the restructuring experience in several jurisdictions and described how, or if, energy-only markets are succeeding in ensuring capacity additions. Supply-side and demand-side mechanisms have been proposed as solutions to address these problems. Theoretical and practical issues of adequacy that are most relevant from a Canadian perspective were presented. In fully developed energy markets, the price of energy reflects scarcity. When generating resources are abundant prices are low. Since investment decisions are based on price expectations, it is unlikely that deregulated markets in their current state can offer adequate generation for the long term. It was concluded that long-term investment will occur with competitive markets and by adding a capacity mechanism to the market design. tabs., figs

The Epidermal Growth Factor Receptor Is a Regulator of Epidermal Complement Component Expression and Complement Activation

DEFF Research Database (Denmark)

Abu-Humaidan, Anas H A; Ananthoju, Nageshwar; Mohanty, Tirthankar

2014-01-01

The complement system is activated in response to tissue injury. During wound healing, complement activation seems beneficial in acute wounds but may be detrimental in chronic wounds. We found that the epidermal expression of many complement components was only increased to a minor extent in skin...

Subversion of complement by hematophagous parasites

OpenAIRE

Schroeder, Hélène; Skelly, Patrick; Zipfel, Peter F.; Losson, Bertrand; Vanderplasschen, Alain

2009-01-01

The complement system is a crucial part of innate and adaptive immunity which exerts a significant evolutionary pressure on pathogens. It has selected for those pathogens, mainly micro-organisms but also parasites, that have evolved countermeasures. The characterization of how pathogens evade complement attack is a rapidly developing field of current research. In recent years, multiple complement evasion strategies have been characterized. In this review, we focus on complement escape mechani...

Deregulation of the arginine deiminase (arc) operon in penicillin-tolerant mutants of Streptococcus gordonii.

Science.gov (United States)

Caldelari, I; Loeliger, B; Langen, H; Glauser, M P; Moreillon, P

2000-10-01

Penicillin tolerance is an incompletely understood phenomenon that allows bacteria to resist drug-induced killing. Tolerance was studied with independent Streptococcus gordonii mutants generated by cyclic exposure to 500 times the MIC of penicillin. Parent cultures lost 4 to 5 log(10) CFU/ml of viable counts/24 h. In contrast, each of four independent mutant cultures lost bacteria and were encoded by an operon that was >80% similar to the arginine-deiminase (arc) operon of these organisms. Partial nucleotide sequencing and insertion inactivation of the S. gordonii arc locus indicated that tolerance was not a direct consequence of arc alteration. On the other hand, genetic transformation of tolerance by Tol1 DNA always conferred arc deregulation. In nontolerant recipients, arc was repressed during exponential growth and up-regulated during postexponential growth. In tolerant transformants, arc was constitutively expressed. Tol1 DNA transformed tolerance at the same rate as transformation of a point mutation (10(-2) to 10(-3)). The tolerance mutation mapped on a specific chromosomal fragment but was physically distant from arc. Importantly, arc deregulation was observed in most (6 of 10) of additional independent penicillin-tolerant mutants. Thus, although not exclusive, the association between arc deregulation and tolerance was not fortuitous. Since penicillin selection mimicked the antibiotic pressure operating in the clinical environment, arc deregulation might be an important correlate of naturally occurring tolerance and help in understanding the mechanism(s) underlying this clinically problematic phenotype.

Cooperation between MASP-1 and MASP-2 in the generation of C3 convertase through the MBL pathway

DEFF Research Database (Denmark)

Møller-Kristensen, Mette; Thiel, Steffen; Sjöholm, Anders

2007-01-01

The complement system is an important part of the innate immune system. Three pathways, the classical, the alternative and the lectin pathway, lead to the cleavage of complement factor C3, a central event in the activation of the complement system. We investigated the deposition of C3b (solid-pha....... Our results demonstrate a function of the orphan protease MASP-1 by providing evidence that this enzyme collaborates with MASP-2 in the generation of C3 convertase, a process observable at high serum concentration, but not at low serum concentration...

Deregulation and restructuring of the electricity sector in Spain

International Nuclear Information System (INIS)

Francia, L.

2000-01-01

This economic analysis of the Electric Power industry and market in Spain shows how the electricity deregulation and liberalization in Spain have given rise to an electricity industry which not only complies in spirit and letter with the E.U. Directive on the internal energy market, but which in fact goes much further. (A.L.B.)

P-I Snake Venom Metalloproteinase Is Able to Activate the Complement System by Direct Cleavage of Central Components of the Cascade

Science.gov (United States)

Pidde-Queiroz, Giselle; Magnoli, Fábio Carlos; Portaro, Fernanda C. V.; Serrano, Solange M. T.; Lopes, Aline Soriano; Paes Leme, Adriana Franco; van den Berg, Carmen W.; Tambourgi, Denise V.

2013-01-01

Background Snake Venom Metalloproteinases (SVMPs) are amongst the key enzymes that contribute to the high toxicity of snake venom. We have recently shown that snake venoms from the Bothrops genus activate the Complement system (C) by promoting direct cleavage of C-components and generating anaphylatoxins, thereby contributing to the pathology and spread of the venom. The aim of the present study was to isolate and characterize the C-activating protease from Bothrops pirajai venom. Results Using two gel-filtration chromatography steps, a metalloproteinase of 23 kDa that activates Complement was isolated from Bothrops pirajai venom. The mass spectrometric identification of this protein, named here as C-SVMP, revealed peptides that matched sequences from the P-I class of SVMPs. C-SVMP activated the alternative, classical and lectin C-pathways by cleaving the α-chain of C3, C4 and C5, thereby generating anaphylatoxins C3a, C4a and C5a. In vivo, C-SVMP induced consumption of murine complement components, most likely by activation of the pathways and/or by direct cleavage of C3, leading to a reduction of serum lytic activity. Conclusion We show here that a P-I metalloproteinase from Bothrops pirajai snake venom activated the Complement system by direct cleavage of the central C-components, i.e., C3, C4 and C5, thereby generating biologically active fragments, such as anaphylatoxins, and by cleaving the C1-Inhibitor, which may affect Complement activation control. These results suggest that direct complement activation by SVMPs may play a role in the progression of symptoms that follow envenomation. PMID:24205428

Learning without experience: Understanding the strategic implications of deregulation and competition in the electricity industry

Energy Technology Data Exchange (ETDEWEB)

Lomi, A. [School of Economics, University of Bologna, Bologna (Italy); Larsen, E.R. [Dept. of Managements Systems and Information, City University Business School, London (United Kingdom)

1998-11-01

As deregulation of the electricity industry continues to gain momentum around the world, electricity companies face unprecedented challenges. Competitive complexity and intensity will increase substantially as deregulated companies find themselves competing in new industries, with new rules, against unfamiliar competitors - and without any history to learn from. We describe the different kinds of strategic issues that newly deregulated utility companies are facing, and the risks that strategic issues implicate. We identify a number of problems induced by experiential learning under conditions of competence-destroying change, and we illustrate ways in which companies can activate history-independent learning processes. We suggest that Micro worlds - a new generation of computer-based learning environments made possible by conceptual and technological progress in the fields of system dynamics and systems thinking - are particularly appropriate tools to accelerate and enhance organizational and managerial learning under conditions of increased competitive complexity. (au)

Intricacies of hedgehog signaling pathways: A perspective in tumorigenesis

International Nuclear Information System (INIS)

Kar, Swayamsiddha; Deb, Moonmoon; Sengupta, Dipta; Shilpi, Arunima; Bhutia, Sujit Kumar; Patra, Samir Kumar

2012-01-01

The hedgehog (HH) signaling pathway is a crucial negotiator of developmental proceedings in the embryo governing a diverse array of processes including cell proliferation, differentiation, and tissue patterning. The overall activity of the pathway is significantly curtailed after embryogenesis as well as in adults, yet it retains many of its functional capacities. However, aberration in HH signaling mediates the initiation, proliferation and continued sustenance of malignancy in different tissues to varying degrees through different mechanisms. In this review, we provide an overview of the role of constitutively active aberrant HH signaling pathway in different types of human cancer and the underlying molecular and genetic mechanisms that drive tumorigenesis in that particular tissue. An insight into the various modes of anomalous HH signaling in different organs will provide a comprehensive knowledge of the pathway in these tissues and open a window for individually tailored, tissue-specific therapeutic interventions. The synergistic cross talking of HH pathway with many other regulatory molecules and developmentally inclined signaling pathways may offer many avenues for pharmacological advances. Understanding the molecular basis of abnormal HH signaling in cancer will provide an opportunity to inhibit the deregulated pathway in many aggressive and therapeutically challenging cancers where promising options are not available.

Intricacies of hedgehog signaling pathways: A perspective in tumorigenesis

Energy Technology Data Exchange (ETDEWEB)

Kar, Swayamsiddha; Deb, Moonmoon; Sengupta, Dipta; Shilpi, Arunima; Bhutia, Sujit Kumar [Epigenetics and Cancer Research Laboratory, Biochemistry and Molecular Biology Group, Department of Life Science, National Institute of Technology, Rourkela, Odisha 769008 (India); Patra, Samir Kumar, E-mail: samirp@nitrkl.ac.in [Epigenetics and Cancer Research Laboratory, Biochemistry and Molecular Biology Group, Department of Life Science, National Institute of Technology, Rourkela, Odisha 769008 (India)

2012-10-01

The hedgehog (HH) signaling pathway is a crucial negotiator of developmental proceedings in the embryo governing a diverse array of processes including cell proliferation, differentiation, and tissue patterning. The overall activity of the pathway is significantly curtailed after embryogenesis as well as in adults, yet it retains many of its functional capacities. However, aberration in HH signaling mediates the initiation, proliferation and continued sustenance of malignancy in different tissues to varying degrees through different mechanisms. In this review, we provide an overview of the role of constitutively active aberrant HH signaling pathway in different types of human cancer and the underlying molecular and genetic mechanisms that drive tumorigenesis in that particular tissue. An insight into the various modes of anomalous HH signaling in different organs will provide a comprehensive knowledge of the pathway in these tissues and open a window for individually tailored, tissue-specific therapeutic interventions. The synergistic cross talking of HH pathway with many other regulatory molecules and developmentally inclined signaling pathways may offer many avenues for pharmacological advances. Understanding the molecular basis of abnormal HH signaling in cancer will provide an opportunity to inhibit the deregulated pathway in many aggressive and therapeutically challenging cancers where promising options are not available.

Did rent deregulation alter tenure choice decisions in the Czech Republic?

Czech Academy of Sciences Publication Activity Database

Tsharakyan, Ashot; Zemčík, Petr

2016-01-01

Roč. 24, č. 2 (2016), s. 335-360 ISSN 0967-0750 Institutional support: PRVOUK-P23 Keywords : Czech Republic * rent regulation and deregulation * real estate prices Subject RIV: AH - Economics Impact factor: 0.479, year: 2016

Complement-coagulation cross-talk: a potential mediator of the physiological activation of complement by low pH

Directory of Open Access Journals (Sweden)

Hany Ibrahim Kenawy

2015-05-01

Full Text Available The complement system is a major constituent of the innate immune system. It not only bridges innate and adaptive arms of the immune system but also links the immune system with the coagulation system. Current understanding of the role of complement has extended far beyond fighting of infections, and now encompasses maintenance of homeostasis, tissue regeneration and pathophysiology of multiple diseases. It has been known for many years that complement activation is strongly pH sensitive, but only relatively recently has the physiological significance of this been appreciated. Most complement assays are carried out at the physiological pH 7.4. However, pH in some extracellular compartments, for example renal tubular fluid in parts of the tubule, and extracellular fluid at inflammation loci, is sufficiently acidic to activate complement. The exact molecular mechanism of this activation is still unclear, but possible cross talk between the contact system and complement may exist at low pH with subsequent complement activation. The current article reviews the published data on the effect of pH on the contact system and complement activity, the nature of the pH sensor molecules, and the clinical implications of these effects. Of particular interest is chronic kidney disease (CKD accompanied by metabolic acidosis, in which therapeutic alkalinisation of urine has been shown significantly to reduce tubular complement activation products, an effect which may have important implications for slowing progression of CKD.

A robust optimization based approach for microgrid operation in deregulated environment

International Nuclear Information System (INIS)

Gupta, R.A.; Gupta, Nand Kishor

2015-01-01

Highlights: • RO based approach developed for optimal MG operation in deregulated environment. • Wind uncertainty modeled by interval forecasting through ARIMA model. • Proposed approach evaluated using two realistic case studies. • Proposed approach evaluated the impact of degree of robustness. • Proposed approach gives a significant reduction in operation cost of microgrid. - Abstract: Micro Grids (MGs) are clusters of Distributed Energy Resource (DER) units and loads. MGs are self-sustainable and generally operated in two modes: (1) grid connected and (2) grid isolated. In deregulated environment, the operation of MG is managed by the Microgrid Operator (MO) with an objective to minimize the total cost of operation. The MG management is crucial in the deregulated power system due to (i) integration of intermittent renewable sources such as wind and Photo Voltaic (PV) generation, and (ii) volatile grid prices. This paper presents robust optimization based approach for optimal MG management considering wind power uncertainty. Time series based Autoregressive Integrated Moving Average (ARIMA) model is used to characterize the wind power uncertainty through interval forecasting. The proposed approach is illustrated through a case study having both dispatchable and non-dispatchable generators through different modes of operation. Further the impact of degree of robustness is analyzed in both cases on the total cost of operation of the MG. A comparative analysis between obtained results using proposed approach and other existing approach shows the strength of proposed approach in cost minimization in MG management

Deregulation of the endogenous C/EBPβ LIP isoform predisposes to tumorigenesis.

Science.gov (United States)

Bégay, Valérie; Smink, Jeske J; Loddenkemper, Christoph; Zimmermann, Karin; Rudolph, Cornelia; Scheller, Marina; Steinemann, Doris; Leser, Ulf; Schlegelberger, Brigitte; Stein, Harald; Leutz, Achim

2015-01-01

Two long and one truncated isoforms (termed LAP*, LAP, and LIP, respectively) of the transcription factor CCAAT enhancer binding protein beta (C/EBPβ) are expressed from a single intronless Cebpb gene by alternative translation initiation. Isoform expression is sensitive to mammalian target of rapamycin (mTOR)-mediated activation of the translation initiation machinery and relayed through an upstream open reading frame (uORF) on the C/EBPβ mRNA. The truncated C/EBPβ LIP, initiated by high mTOR activity, has been implied in neoplasia, but it was never shown whether endogenous C/EBPβ LIP may function as an oncogene. In this study, we examined spontaneous tumor formation in C/EBPβ knockin mice that constitutively express only the C/EBPβ LIP isoform from its own locus. Our data show that deregulated C/EBPβ LIP predisposes to oncogenesis in many tissues. Gene expression profiling suggests that C/EBPβ LIP supports a pro-tumorigenic microenvironment, resistance to apoptosis, and alteration of cytokine/chemokine expression. The results imply that enhanced translation reinitiation of C/EBPβ LIP promotes tumorigenesis. Accordingly, pharmacological restriction of mTOR function might be a therapeutic option in tumorigenesis that involves enhanced expression of the truncated C/EBPβ LIP isoform. Elevated C/EBPβ LIP promotes cancer in mice. C/EBPβ LIP is upregulated in B-NHL. Deregulated C/EBPβ LIP alters apoptosis and cytokine/chemokine networks. Deregulated C/EBPβ LIP may support a pro-tumorigenic microenvironment.

Deregulation experiences in Alberta and Ontario

International Nuclear Information System (INIS)

Axford, D.

2003-01-01

A brief introduction of Nexen Chemicals, one of the largest producers of sodium chlorate in the world, was offered, and a map displaying its locations throughout the world was displayed. Nexen is one of Canada's largest independent oil and gas producers, while Nexen Marketing is involved in the marketing of natural gas in North America. In January 2001, the deregulated market opened in Alberta. High natural gas prices, generation shortages, high prices in California and an upcoming provincial election all combined to complicate the situation. A high degree of volatility characterized the market. A chart displaying weekly average Alberta power and gas prices from Jan 2002 to 13 Oct 2002 was shown. In Ontario, the market opened in May 2002, and the demand growth rate was in the 1 to 2 per cent range. The author indicated that approximately 20 per cent of homeowners in Ontario have signed deals with retailers, contrary to Alberta where very few have done so. A similar chart displaying weekly average Ontario power prices was presented. The issues in Ontario are: consistency in policy, increase market transparency, transmission / distribution price flexibility, overall transmission / distribution to industrial consumers high, and increasing costs of the system operator. In Alberta, the issues are: government intent, congestion management issues, and billing settlement errors that continue. The opportunities offered by a deregulated market include process responsiveness which is rewarded, the ability to look in forward prices when prices fit margin requirement, and gives companies the opportunity to participate in the development of the market. Various charts were also displayed to further illustrate the market in both Alberta and Ontario. figs

Global Autorecognition and Activation of Complement by Mannan-Binding Lectin in a Mouse Model of Type 1 Diabetes

Directory of Open Access Journals (Sweden)

Esben Axelgaard

2017-01-01

Full Text Available Increasing evidence links mannan-binding lectin (MBL to late vascular complications of diabetes. MBL is a complement-activating pattern recognition molecule of the innate immune system that can mediate an inflammation response through activation of the lectin pathway. In two recent animal studies, we have shown that autoreactivity of MBL is increased in the kidney in diabetic nephropathy. We hypothesize that long-term exposure to uncontrolled high blood glucose in diabetes may mediate formation of neoepitopes in several tissues and that MBL is able to recognize these structures and thus activate the lectin pathway. To test this hypothesis, we induced diabetes by injection of low-dose streptozotocin in MBL double-knockout (MBL/DKO mice. Development of diabetes was followed by measurements of blood glucose and urine albumin-to-creatinine ratio. Fluorophore-labelled recombinant MBL was injected intravenously in diabetic and nondiabetic mice followed by ex vivo imaging of several organs. We observed that MBL accumulated in the heart, liver, brain, lung, pancreas, and intestines of diabetic mice. We furthermore detected increased systemic complement activation after administration of MBL, thus indicating MBL-mediated systemic complement activation in these animals. These new findings indicate a global role of MBL during late diabetes-mediated vascular complications in various tissues.

Core designs for the de-regulated market

International Nuclear Information System (INIS)

Almberger, J.; Bernro, R.; Pettersson, H.

1999-01-01

Complete text of publication follows: The electricity market deregulation in the Nordic countries encourages innovations and cost reductions for power production in the Vattenfall reactors. The competition on the electricity market is strong, electricity price reductions dramatic and uncertainties about the future power demand is large. In the fuel area this situation has given increased attention to traditional areas like flexibility in power production, improved core designs, need for margins (improved fuel designs), improved surveillance, decreased lead times. At Vattenfall new fuel designs are already being implemented following the last fuel purchase, for which flexibility and margins, were given high values in the evaluations with the multipurpose task of eliminating fuel related problems and meeting the future market situation. This strategy has given Vattenfall a flying start to meeting the demands of the de-regulated market. What has been added are broad studies undertaken to investigate the various route into the future with respect to finding the most effective strategies for fuel and core design and optimization. In the present paper the Vattenfall priorities for fuel designs and margins are presented in a schematic manner summarizing the results of the last fuel purchase and also presenting the current program for LFAs. Technical limitations, licensing and R and D aspects, with respect to improving the fuel utilization will be mentioned. The main focus in the paper is on the broad study carried out in the PWR core design area. Driven by the relatively low power demand various possibilities for higher production flexibility have been investigated specifically extended coast-down, coast-up and yearly load follow. Further to reduce the costs for fuel consumption improvements in core designs have been studied: improved low leakage loading patterns, low enriched end zones, improved Gd designs etc. Main results and conclusions of the core design studies will

A dynamic approach for the optimal electricity dispatch in the deregulated market

International Nuclear Information System (INIS)

Carraretto, Cristian; Lazzaretto, Andrea

2004-01-01

The electricity market has been experiencing the deregulation process in many countries. Effective approaches to the management of single power plants or groups of plants are therefore becoming crucial for the competitiveness of energy utilities. A dynamic programming approach is presented in this paper for the optimal plant management in the new Italian deregulated market. A thorough description of the method is given in cases of free or fixed production over time (e.g. when the overall production is limited by bilateral contracts or cogeneration). Analysis of market characteristics, detailed thermodynamic models of plant operation and reliable price forecasts over the time period of interest are required. The suggested approach is useful for both long-term scheduling and planning daily offers in the market

GLUCOCORTICOSTEROIDS' EFFECT UPON THE COMPLEMENT LEVEL

Directory of Open Access Journals (Sweden)

Voja Pavlovic

2001-03-01

Full Text Available The effect of high doses of cortisol upon the level of the overall complements'hemolytic activity and particular complements' components is studies. The experimentsinvolved guinea pigs of male sex of the body mass from 300 to 400 g, namelythose that have not been treated by anything so far. The doses of hydrocortisone(Hemofarm DD were also used for the experiment. The overall complements'activity was determined by testing the capabilities of a series of various solutions ofthe guinea pigs' serum to separate sheep erythrocytes that were made sensitive byrabbit anti-erythrocyte antibodies. The determination of the C1, C2, C3 and C4complements' components was done by the method of the quantitative diffusion ofthe radial type by using the Partigen blocks Behringwerke AG. The series comprised25 guinea pigs of male sex. The low cortisol level rapidly increase the overallhemolytic activity of the complements of the C1 est erase concentration. Along withthe cortisol dose increase the overall hemolytic complements' activity is dropping aswell as that of the C1, C2, C3 and C4 complements' components.

CipA of Acinetobacter baumannii Is a Novel Plasminogen Binding and Complement Inhibitory Protein.

Science.gov (United States)

Koenigs, Arno; Stahl, Julia; Averhoff, Beate; Göttig, Stephan; Wichelhaus, Thomas A; Wallich, Reinhard; Zipfel, Peter F; Kraiczy, Peter

2016-05-01

Acinetobacter baumannii is an emerging opportunistic pathogen, responsible for up to 10% of gram-negative, nosocomial infections. The global increase of multidrug-resistant and pan-resistant Acinetobacter isolates presents clinicians with formidable challenges. To establish a persistent infection,A. baumannii must overcome the detrimental effects of complement as the first line of defense against invading microorganisms. However, the immune evasion principles underlying serum resistance inA. baumannii remain elusive. Here, we identified a novel plasminogen-binding protein, termed CipA. Bound plasminogen, upon conversion to active plasmin, degraded fibrinogen and complement C3b and contributed to serum resistance. Furthermore, CipA directly inhibited the alternative pathway of complement in vitro, irrespective of its ability to bind plasminogen. A CipA-deficient mutant was efficiently killed by human serum and showed a defect in the penetration of endothelial monolayers, demonstrating that CipA is a novel multifunctional protein that contributes to the pathogenesis ofA. baumannii. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Zap... Alberta is jolted by electric deregulation

International Nuclear Information System (INIS)

Howe, M.E.

2001-01-01

Of all Canadian provinces, Alberta has travelled the furthest along the electric deregulation road. On January 1, 2001, full retail competition came into effect. Wholesale electricity prices are set by the province through an auction process. The bids from purchasers are made through the Power Pool of Alberta against supply offers. Power prices increased from being amongst the lowest in the world to being amongst the highest in North America as a result of deregulation. Changes to the Electric Utilities Act were made recently by the Alberta government to try to mitigate the factors affecting power price increases. RBC Dominion Securities is of the opinion that the changes will not significantly impact the Alberta Pool Price. It is expected that the trend for power price increases to continue, despite some relief from relatively low-cost electricity being felt by other Canadian provinces as a result of the energy crisis in North America. Based on the Electric Competition Unfolds in Alberta report dated June 2, 2001 prepared by RBC Dominion Securities, this document examines the factors at play in electric price increases, assess the sustainability of current power prices in Alberta, and identify Canadian companies believed to be best positioned in the pipeline and gas and electric sectors to benefit from the high power prices in Alberta. Those companies were ATCO, Canadian Utilities, Westcoast Energy and TransCanada PipeLines, and TransAlta. 5 tabs., 5 figs

Steady state security assessment in deregulated power systems

Science.gov (United States)

Manjure, Durgesh Padmakar

Power system operations are undergoing changes, brought about primarily due to deregulation and subsequent restructuring of the power industry. The primary intention of the introduction of deregulation in power systems was to bring about competition and improved customer focus. The underlying motive was increased economic benefit. Present day power system analysis is much different than what it was earlier, essentially due to the transformation of the power industry from being cost-based to one that is price-based and due to open access of transmission networks to the various market participants. Power is now treated as a commodity and is traded in an open market. The resultant interdependence of the technical criteria and the economic considerations has only accentuated the need for accurate analysis in power systems. The main impetus in security analysis studies is on efficient assessment of the post-contingency status of the system, accuracy being of secondary consideration. In most cases, given the time frame involved, it is not feasible to run a complete AC load flow for determining the post-contingency state of the system. Quite often, it is not warranted as well, as an indication of the state of the system is desired rather than the exact quantification of the various state variables. With the inception of deregulation, transmission networks are subjected to a host of multilateral transactions, which would influence physical system quantities like real power flows, security margins and voltage levels. For efficient asset utilization and maximization of the revenue, more often than not, transmission networks are operated under stressed conditions, close to security limits. Therefore, a quantitative assessment of the extent to which each transaction adversely affects the transmission network is required. This needs to be done accurately as the feasibility of the power transactions and subsequent decisions (execution, curtailment, pricing) would depend upon the

Transposable Element Misregulation Is Linked to the Divergence between Parental piRNA Pathways in Drosophila Hybrids.

Science.gov (United States)

Romero-Soriano, Valèria; Modolo, Laurent; Lopez-Maestre, Hélène; Mugat, Bruno; Pessia, Eugénie; Chambeyron, Séverine; Vieira, Cristina; Garcia Guerreiro, Maria Pilar

2017-06-01

Interspecific hybridization is a genomic stress condition that leads to the activation of transposable elements (TEs) in both animals and plants. In hybrids between Drosophila buzzatii and Drosophila koepferae, mobilization of at least 28 TEs has been described. However, the molecular mechanisms underlying this TE release remain poorly understood. To give insight on the causes of this TE activation, we performed a TE transcriptomic analysis in ovaries (notorious for playing a major role in TE silencing) of parental species and their F1 and backcrossed (BC) hybrids. We find that 15.2% and 10.6% of the expressed TEs are deregulated in F1 and BC1 ovaries, respectively, with a bias toward overexpression in both cases. Although differences between parental piRNA (Piwi-interacting RNA) populations explain only partially these results, we demonstrate that piRNA pathway proteins have divergent sequences and are differentially expressed between parental species. Thus, a functional divergence of the piRNA pathway between parental species, together with some differences between their piRNA pools, might be at the origin of hybrid instabilities and ultimately cause TE misregulation in ovaries. These analyses were complemented with the study of F1 testes, where TEs tend to be less expressed than in D. buzzatii. This can be explained by an increase in piRNA production, which probably acts as a defence mechanism against TE instability in the male germline. Hence, we describe a differential impact of interspecific hybridization in testes and ovaries, which reveals that TE expression and regulation are sex-biased. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Impacts of Contingency Reserve on Nodal Price and Nodal Reliability Risk in Deregulated Power Systems

DEFF Research Database (Denmark)

Zhao, Qian; Wang, Peng; Goel, Lalit

2013-01-01

The deregulation of power systems allows customers to participate in power market operation. In deregulated power systems, nodal price and nodal reliability are adopted to represent locational operation cost and reliability performance. Since contingency reserve (CR) plays an important role...... in reliable operation, the CR commitment should be considered in operational reliability analysis. In this paper, a CR model based on customer reliability requirements has been formulated and integrated into power market settlement. A two-step market clearing process has been proposed to determine generation...

Efficiency in the United States electric industry: Transaction costs, deregulation, and governance structures

Science.gov (United States)

Peterson, Carl

Transaction costs economics (TCE) posits that firms have an incentive to bypass the market mechanisms in situations where the cost of using the market is prohibitive. Vertical integration, among other governance mechanisms, can be used to minimize the transactions costs associated with the market mechanism. The study analyses different governance mechanisms, which range from complete vertical integration to the use of market mechanisms, for firms in the US electric sector. This sector has undergone tremendous change in the past decade including the introduction of retail competition in some jurisdictions. As a result of the push toward deregulation of the industry, vertically integration, while still significant in the sector, has steadily been replaced by alternative governance structures. Using a sample of 136 investor-owned electric utilities that reported data the US Federal Energy Regulatory Commission between 1996 and 2002, this study estimates firm level efficiency using Data Envelopment Analysis (DEA) and relates these estimates to governance structure and public policies. The analysis finds that vertical integration is positively related to firm efficiency, although in a non-linear fashion suggesting that hybrid governance structures tend to be associated with lower efficiency scores. In addition, while some evidence is found for negative short-term effects on firm efficiency from the choice to deregulate, this result is sensitive to DEA model choice. Further, competition in retail markets is found to be positively related to firm level efficiency, but the retreat from deregulation, which occurred after 2000, is negatively associated with firm-level efficiency. These results are important in the ongoing academic and public policy debates concerning deregulation of the electric section and indicate that vertical economies remain in the industry, but that competition has provided incentives for improving firm level efficiency.

Deregulation and internationalisation - impact on the Swedish nuclear industry

International Nuclear Information System (INIS)

Haukeland, Sverre R.

2010-01-01

The deregulation of the Swedish electricity market in 1996 was well known in advance, and the nuclear power plants in Sweden, as well as their main suppliers, made early preparations for a this new situation. In a study - performed by the author at Malardalen University in Sweden - it is concluded that the electricity industry, including the nuclear power plants, was fundamentally transformed in conjunction with market liberalisation. Two large foreign companies, E-on and Fortum, entered the Swedish market and became part-owners of the nuclear plants. After deregulation, the electricity market in Sweden is dominated by these two companies and the large national company Vattenfall. Similarly, Vattenfall has recently grown into an international energy company, acquiring generation capacity in Northern Europe outside of Sweden, including nuclear power plants in Germany. Restructuring of the nuclear industry on the supplier side started in the 1980's, when the Swedish company ASEA and BBC of Switzerland merged to become ABB. Several years later the Swedish nuclear plant supplier ABB-Atom became part of Westinghouse Electric Company, today owned by Toshiba. The Swedish experience thus confirms an international trend of mergers and consolidation in the nuclear industry. (authors)

Complement activation by Pseudomonas aeruginosa biofilms

DEFF Research Database (Denmark)

Jensen, E T; Kharazmi, A; Garred, P

1993-01-01

In chronic infections, such as the bronchopulmonary Pseudomonas aeruginosa infection in cystic fibrosis (CF) patients, bacteria persist despite an intact host immune defense and frequent antibiotic treatment. An important reason for the persistence of the bacteria is their capacity for the biofilm...... mode of growth. In this study we investigated the role of biofilms in activation of complement, a major contributor to the inflammatory process. Complement activation by P. aeruginosa was examined in a complement consumption assay, production of C3 and factor B conversion products assessed by crossed...... immuno-electrophoresis, C5a generation tested by a PMN chemotactic assay, and terminal complement complex formation measured by ELISA. Two of the four assays showed that P. aeruginosa grown in biofilm activated complement less than planktonic bacteria, and all assays showed that activation by intact...

Small molecule screening identifies targetable zebrafish pigmentation pathways

DEFF Research Database (Denmark)

Colanesi, Sarah; Taylor, Kerrie L; Temperley, Nicholas D

2012-01-01

Small molecules complement genetic mutants and can be used to probe pigment cell biology by inhibiting specific proteins or pathways. Here, we present the results of a screen of active compounds for those that affect the processes of melanocyte and iridophore development in zebrafish and investig......Small molecules complement genetic mutants and can be used to probe pigment cell biology by inhibiting specific proteins or pathways. Here, we present the results of a screen of active compounds for those that affect the processes of melanocyte and iridophore development in zebrafish...... and investigate the effects of a few of these compounds in further detail. We identified and confirmed 57 compounds that altered pigment cell patterning, number, survival, or differentiation. Additional tissue targets and toxicity of small molecules are also discussed. Given that the majority of cell types...

Exploration of Deregulated Long Non-Coding RNAs in Association with Hepatocarcinogenesis and Survival

Energy Technology Data Exchange (ETDEWEB)

Shen, Jing, E-mail: js2182@cumc.columbia.edu [Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University Medical Center, New York, NY 10032 (United States); Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032 (United States); Siegel, Abby B. [Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032 (United States); Department of Medicine, Columbia University Medical Center, New York, NY 10032 (United States); Remotti, Helen [Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032 (United States); Wang, Qiao; Shen, Yueyue [Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University Medical Center, New York, NY 10032 (United States); Santella, Regina M. [Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University Medical Center, New York, NY 10032 (United States); Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032 (United States)

2015-09-10

Long non-coding RNAs (lncRNAs) are larger than 200 nucleotides in length and pervasively expressed across the genome. An increasing number of studies indicate that lncRNA transcripts play integral regulatory roles in cellular growth, division, differentiation and apoptosis. Deregulated lncRNAs have been observed in a variety of human cancers, including hepatocellular carcinoma (HCC). We determined the expression profiles of 90 lncRNAs for 65 paired HCC tumor and adjacent non-tumor tissues, and 55 lncRNAs were expressed in over 90% of samples. Eight lncRNAs were significantly down-regulated in HCC tumor compared to non-tumor tissues (p < 0.05), but no lncRNA achieved statistical significance after Bonferroni correction for multiple comparisons. Within tumor tissues, carrying more aberrant lncRNAs (6–7) was associated with a borderline significant reduction in survival (HR = 8.5, 95% CI: 1.0–72.5). The predictive accuracy depicted by the AUC was 0.93 for HCC survival when using seven deregulated lncRNAs (likelihood ratio test p = 0.001), which was similar to that combining the seven lncRNAs with tumor size and treatment (AUC = 0.96, sensitivity = 87%, specificity = 87%). These data suggest the potential association of deregulated lncRNAs with hepatocarcinogenesis and HCC survival.

Transmission investment and planning in deregulated market environment : a literature survey (part 1)

International Nuclear Information System (INIS)

Wen, F.; Wu, F.F.

2005-01-01

This paper is the first half of a 2-part paper that provided details of a comprehensive survey of issues related to transmission investment and expansion planning in the electricity market. The lack of adequate transmission capacity has played an important role in recent power crises, and deregulation has had a significant impact on the investment and planning process of transmission systems. The main objective of transmission investment is to meet load demands as cheaply as possible. In a deregulated market, there is no longer centrally coordinated planning of new generation. Transmission planning is generally not coordinated with generation planning. There is considerable uncertainty with regard to transmission capacity requirements due to long lead times for transmission construction. Generating plants and transmission lines are built according to investor assessments and private interests, and current transmission systems were not designed to handle supply and demand patterns in competitive markets. It was recommended that new transmission plans should meet reliability requirements while minimizing expected unserved energy. It was concluded that reliability criteria must be redefined to account for the fact that transmission systems are more stressed under deregulation. Two popular financial transmission rights were also discussed, notably (1) point-to-point financial transmission rights (FTR); and (2) financial flowgate rights (FGR)

CL-L1 and CL-K1 and other complement associated pattern recognition molecules in systemic lupus erythematosus

DEFF Research Database (Denmark)

Troldborg, Anne; Thiel, Steffen; Jensen, Lisbeth

2015-01-01

The objective of this study was to explore the involvement of collectin liver 1 (CL-L1) and collectin kidney 1 (CL-K1) and other pattern recognition molecules (PRMs) of the lectin pathway of the complement system in a cross-sectional cohort of systemic lupus erythematosus (SLE) patients...

Deregulation of a STAT3-IL8 Signaling Pathway Promotes Human Glioblastoma Cell Proliferation and Invasiveness

Science.gov (United States)

de la Iglesia, Núria; Konopka, Genevieve; Lim, Kah Leong; Nutt, Catherine L.; Bromberg, Jacqueline F.; Frank, David A.; Mischel, Paul S.; Louis, David N.; Bonni, Azad

2009-01-01

Inactivation of the tumor suppressor PTEN is recognized as a major event in the pathogenesis of the brain tumor glioblastoma. However, the mechanisms by which PTEN loss specifically impacts the malignant behavior of glioblastoma cells including their proliferation and propensity for invasiveness remain poorly understood. Genetic studies suggest that the transcription factor STAT3 harbors a PTEN-regulated tumor suppressive function in mouse astrocytes. Here, we report that STAT3 plays a critical tumor suppressive role in PTEN-deficient human glioblastoma cells. Endogenous STAT3 signaling is specifically inhibited in PTEN-deficient glioblastoma cells. Strikingly, reactivation of STAT3 in PTEN-deficient glioblastoma cells inhibits their proliferation, invasiveness, and ability to spread on myelin. We also identify the chemokine IL8 as a novel target gene of STAT3 in human glioblastoma cells. Activated STAT3 occupies the endogenous IL8 promoter and directly represses IL8 transcription. Consistent with these results, IL8 is upregulated in PTEN-deficient human glioblastoma tumors. Importantly, IL8 repression mediates STAT3-inhibition of glioblastoma cell proliferation, invasiveness, and spreading on myelin. Collectively, our findings uncover a novel link between STAT3 and IL8 whose deregulation plays a key role in the malignant behavior of PTEN-deficient glioblastoma cells. These studies suggest that STAT3 activation or IL8 inhibition may have potential in patient-tailored treatment of PTEN-deficient brain tumors. PMID:18524891

A tick mannose-binding lectin inhibitor interferes with the vertebrate complement cascade to enhance transmission of the lyme disease agent

NARCIS (Netherlands)

Schuijt, Tim J.; Coumou, Jeroen; Narasimhan, Sukanya; Dai, Jianfeng; Deponte, Kathleen; Wouters, Diana; Brouwer, Mieke; Oei, Anneke; Roelofs, Joris J. T. H.; van Dam, Alje P.; van der Poll, Tom; van't Veer, Cornelis; Hovius, Joppe W.; Fikrig, Erol

2011-01-01

The Lyme disease agent Borrelia burgdorferi is primarily transmitted to vertebrates by Ixodes ticks. The classical and alternative complement pathways are important in Borrelia eradication by the vertebrate host. We recently identified a tick salivary protein, designated P8, which reduced

Pathogens' toolbox to manipulate human complement.

Science.gov (United States)

Fernández, Francisco J; Gómez, Sara; Vega, M Cristina

2017-12-14

The surveillance and pathogen fighting functions of the complement system have evolved to protect mammals from life-threatening infections. In turn, pathogens have developed complex molecular mechanisms to subvert, divert and evade the effector functions of the complement. The study of complement immunoevasion by pathogens sheds light on their infection drivers, knowledge that is essential to implement therapies. At the same time, complement evasion also acts as a discovery ground that reveals important aspects of how complement works under physiological conditions. In recent years, complex interrelationships between infection insults and the onset of autoimmune and complement dysregulation diseases have led to propose that encounters with pathogens can act as triggering factors for disease. The correct management of these diseases involves the recognition of their triggering factors and the development and administration of complement-associated molecular therapies. Even more recently, unsuspected proteins from pathogens have been shown to possess moonlighting functions as virulence factors, raising the possibility that behind the first line of virulence factors there be many more pathogen proteins playing secondary, helping and supporting roles for the pathogen to successfully establish infections. In an era where antibiotics have a progressively reduced effect on the management and control of infectious diseases worldwide, knowledge on the mechanisms of pathogenic invasion and evasion look more necessary and pressing than ever. Copyright © 2017 Elsevier Ltd. All rights reserved.

Bluewater Power goes ERP route to address deregulation : case study

Energy Technology Data Exchange (ETDEWEB)

Broad, K. [Bluewater Power Distribution Corp., Sarnia, ON (Canada)

2009-05-15

Bluewater Power Distribution Corporation distributes electricity to 35,000 customers in southwestern Ontario, including residential customers, large industries and commercial establishments. Their distribution system network consists of more than 344 miles of overhead wires and 125 miles of underground wires. The company employs more than 90 full-time people and is the result of a merger of six local utilities in year 2000. Ontario's energy market was preparing to deregulate at the time of the merger. Under the deregulation rules, utilities in the province were required to provide unbundled bills and exchange customer electronic business transactions with energy retailers. New rules opened up the cost of power on the wholesale side, requiring utilities to conduct wholesale settlements with the Independent Electricity System Operator (IESO). The IESO manages Ontario's bulk electricity power system and operates the wholesale market. This article described the solution that Bluewater Power's information technology (IT) team found to support Ontario's local market, meet regulatory demands and adapt to future regulatory changes.

Maintenance cost models in deregulated power systems under opportunity costs

International Nuclear Information System (INIS)

Al-Arfaj, K.; Dahal, K.; Azaiez, M.N.

2007-01-01

In a centralized power system, the operator is responsible for scheduling maintenance. There are different types of maintenance, including corrective maintenance; predictive maintenance; preventive maintenance; and reliability-centred maintenance. The main cause of power failures is poor maintenance. As such, maintenance costs play a significant role in deregulated power systems. They include direct costs associated with material and labor costs as well as indirect costs associated with spare parts inventory, shipment, test equipment, indirect labor, opportunity costs and cost of failure. In maintenance scheduling and planning, the cost function is the only component of the objective function. This paper presented the results of a study in which different components of maintenance costs were modeled. The maintenance models were formulated as an optimization problem with single and multiple objectives and a set of constraints. The maintenance costs models could be used to schedule the maintenance activities of power generators more accurately and to identify the best maintenance strategies over a period of time as they consider failure and opportunity costs in a deregulated environment. 32 refs., 4 tabs., 4 figs

Complement System Part II: Role in Immunity

Science.gov (United States)

Merle, Nicolas S.; Noe, Remi; Halbwachs-Mecarelli, Lise; Fremeaux-Bacchi, Veronique; Roumenina, Lubka T.

2015-01-01

The complement system has been considered for a long time as a simple lytic cascade, aimed to kill bacteria infecting the host organism. Nowadays, this vision has changed and it is well accepted that complement is a complex innate immune surveillance system, playing a key role in host homeostasis, inflammation, and in the defense against pathogens. This review discusses recent advances in the understanding of the role of complement in physiology and pathology. It starts with a description of complement contribution to the normal physiology (homeostasis) of a healthy organism, including the silent clearance of apoptotic cells and maintenance of cell survival. In pathology, complement can be a friend or a foe. It acts as a friend in the defense against pathogens, by inducing opsonization and a direct killing by C5b–9 membrane attack complex and by triggering inflammatory responses with the anaphylatoxins C3a and C5a. Opsonization plays also a major role in the mounting of an adaptive immune response, involving antigen presenting cells, T-, and B-lymphocytes. Nevertheless, it can be also an enemy, when pathogens hijack complement regulators to protect themselves from the immune system. Inadequate complement activation becomes a disease cause, as in atypical hemolytic uremic syndrome, C3 glomerulopathies, and systemic lupus erythematosus. Age-related macular degeneration and cancer will be described as examples showing that complement contributes to a large variety of conditions, far exceeding the classical examples of diseases associated with complement deficiencies. Finally, we discuss complement as a therapeutic target. PMID:26074922

Borrelia burgdorferi outer surface protein C (OspC) binds complement component C4b and confers bloodstream survival.

Science.gov (United States)

Caine, Jennifer A; Lin, Yi-Pin; Kessler, Julie R; Sato, Hiromi; Leong, John M; Coburn, Jenifer

2017-12-01

Borrelia burgdorferi (Bb) is the causative agent of Lyme disease in the United States, a disease that can result in carditis, and chronic and debilitating arthritis and/or neurologic symptoms if left untreated. Bb survives in the midgut of the Ixodes scapularis tick, or within tissues of immunocompetent hosts. In the early stages of infection, the bacteria are present in the bloodstream where they must resist clearance by the innate immune system of the host. We have found a novel role for outer surface protein C (OspC) from B. burgdorferi and B. garinii in interactions with the complement component C4b and bloodstream survival in vivo. Our data show that OspC inhibits the classical and lectin complement pathways and competes with complement protein C2 for C4b binding. Resistance to complement is important for maintenance of the lifecycle of Bb, enabling survival of the pathogen within the host as well as in the midgut of a feeding tick when ospC expression is induced. © 2017 John Wiley & Sons Ltd.

Human neutrophil peptides and complement factor Bb in pathogenesis of acquired thrombotic thrombocytopenic purpura.

Science.gov (United States)

Cao, Wenjing; Pham, Huy P; Williams, Lance A; McDaniel, Jenny; Siniard, Rance C; Lorenz, Robin G; Marques, Marisa B; Zheng, X Long

2016-11-01

Acquired thrombotic thrombocytopenic purpura is primarily caused by the deficiency of plasma ADAMTS13 activity resulting from autoantibodies against ADAMTS13. However, ADAMTS13 deficiency alone is often not sufficient to cause acute thrombotic thrombocytopenic purpura. Infections or systemic inflammation may precede acute bursts of the disease, but the underlying mechanisms are not fully understood. Herein, 52 patients with acquired autoimmune thrombotic thrombocytopenic purpura and 30 blood donor controls were recruited for the study. The plasma levels of human neutrophil peptides 1-3 and complement activation fragments (i.e. Bb, iC3b, C4d, and sC5b-9) were determined by enzyme-linked immunosorbent assays. Univariate analyses were performed to determine the correlation between each biomarker and clinical outcomes. We found that the plasma levels of human neutrophil peptides 1-3 and Bb in patients with acute thrombotic thrombocytopenic purpura were significantly higher than those in the control (Ppurpura patients and the control. We conclude that innate immunity, i.e. neutrophil and complement activation via the alternative pathway, may play a role in the pathogenesis of acute autoimmune thrombotic thrombocytopenic purpura, and a therapy targeted at these pathways may be considered in a subset of these patients. Copyright© Ferrata Storti Foundation.

Radioassays for quantitation of intact complement proteins C2 and B in human serum

Energy Technology Data Exchange (ETDEWEB)

Oglesby, T J; Ueda, A; Volanakis, J E

1988-05-25

Availability of polyclonal and monoclonal antibodies recognizing determinants on the major cleavage fragments of complement proteins C2 and B enabled development of sensitive radioassays which can be used to quantitate the intact proteins in human sera. Changes in C2 and B concentrations indicative of classical or alternative pathway activation, or both, were seen in normal serum after incubation with complement activators. The authors determined the normal range of C2 concentration to be 11-35 ..mu..g/ml in 32 healthy individuals, and that of protein B to be 74-286 ..mu..g/ml. Sera from patients with systemic lupus erythematosus (SLE), septic shock, infections, and following orthopedic surgery were then assayed. Mean protein B concentration was significantly higher in SLE sera and in the infected and post-operative sera, and the mean C2 concentration in the septic shock group was significantly lower than the mean of healthy individuals. Intact C2 was not detected in known C2-deficient individuals. These assays allow parallel quantitation of the structurally and functionally homologous proteins of the classical (C2) and alternative (B) pathways, which is of interest in patients with genetic and acquired hypocomplementemia. 22 refs.; 3 figs.

Different gene-expression profiles for the poorly differentiated carcinoma and the highly differentiated papillary adenocarcinoma in mammary glands support distinct metabolic pathways

International Nuclear Information System (INIS)

Eilon, Tali; Barash, Itamar

2008-01-01

Deregulation of Stat5 in the mammary gland of transgenic mice causes tumorigenesis. Poorly differentiated carcinoma and highly differentiated papillary adenocarcinoma tumors evolve. To distinguish the genes and elucidate the cellular processes and metabolic pathways utilized to preserve these phenotypes, gene-expression profiles were analyzed. Mammary tumors were excised from transgenic mice carrying a constitutively active variant of Stat5, or a Stat5 variant lacking s transactivation domain. These tumors displayed either the carcinoma or the papillary adenocarcinoma phenotypes. cRNAs, prepared from each tumor were hybridized to an Affymetrix GeneChip ® Mouse Genome 430A 2.0 array. Gene-ontology analysis, hierarchical clustering and biological-pathway analysis were performed to distinct the two types of tumors. Histopathology and immunofluorescence staining complemented the comparison between the tumor phenotypes. The nucleus-cytoskeleton-plasma membrane axis is a major target for differential gene expression between phenotypes. In the carcinoma, stronger expression of genes coding for specific integrins, cytoskeletal proteins and calcium-binding proteins highlight cell-adhesion and motility features of the tumor cells. This is supported by the higher expression of genes involved in O-glycan synthesis, TGF-β, activin, their receptors and Smad3, as well as the Notch ligands and members of the γ-secretase complex that enable Notch nuclear localization. The Wnt pathway was also a target for differential gene expression. Higher expression of genes encoding the degradation complex of the canonical pathway and limited TCF expression in the papillary adenocarcinoma result in membranal accumulation of β-catenin, in contrast to its nuclear translocation in the carcinoma. Genes involved in cell-cycle arrest at G1 and response to DNA damage were more highly expressed in the papillary adenocarcinomas, as opposed to favored G2/M regulation in the carcinoma tumors. At least

Angiogenic factor imbalance precedes complement deposition in placentae of the BPH/5 model of preeclampsia.

Science.gov (United States)

Sones, Jennifer L; Merriam, Audrey A; Seffens, Angelina; Brown-Grant, Dex-Ann; Butler, Scott D; Zhao, Anna M; Xu, Xinjing; Shawber, Carrie J; Grenier, Jennifer K; Douglas, Nataki C

2018-05-01

Preeclampsia (PE), a hypertensive disorder of pregnancy, is a leading cause of maternal and fetal morbidity and mortality. Although the etiology is unknown, PE is thought to be caused by defective implantation and decidualization in pregnancy. Pregnant blood pressure high (BPH)/5 mice spontaneously develop placentopathies and maternal features of human PE. We hypothesized that BPH/5 implantation sites have transcriptomic alterations. Next-generation RNA sequencing of implantation sites at peak decidualization, embryonic day (E)7.5, revealed complement gene up-regulation in BPH/5 vs. controls. In BPH/5, expression of complement factor 3 was increased around the decidual vasculature of E7.5 implantation sites and in the trophoblast giant cell layer of E10.5 placentae. Altered expression of VEGF pathway genes in E5.5 BPH/5 implantation sites preceded complement dysregulation, which correlated with abnormal vasculature and increased placental growth factor mRNA and VEGF 164 expression at E7.5. By E10.5, proangiogenic genes were down-regulated, whereas antiangiogenic sFlt-1 was up-regulated in BPH/5 placentae. We found that early local misexpression of VEGF genes and abnormal decidual vasculature preceded sFlt-1 overexpression and increased complement deposition in BPH/5 placentae. Our findings suggest that abnormal decidual angiogenesis precedes complement activation, which in turn contributes to the aberrant trophoblast invasion and poor placentation that underlie PE.-Sones, J. L., Merriam, A. A., Seffens, A., Brown-Grant, D.-A., Butler, S. D., Zhao, A. M., Xu, X., Shawber, C. J., Grenier, J. K., Douglas, N. C. Angiogenic factor imbalance precedes complement deposition in placentae of the BPH/5 model of preeclampsia.

The issue of natural gas deregulation has arrived on Canada's east coast

Energy Technology Data Exchange (ETDEWEB)

Anon.

2000-06-01

It is predicted that the introduction of natural gas to Atlantic Canada from Nova Scotia's Sable Offshore Energy Project, will usher in an era of competition among suppliers and choice for customers, making gas deregulation a likely development. Natural gas from the Sable Project is regulated by the National Energy Board for such things as tolls and the cost of transmission through the Maritimes and Northeast Pipeline; residential customer service will be provided by Sempra Atlantic Gas, a provincially regulated distributor which holds the franchise to service the entire province with a gas transportation network. Sempra will provide the infrastructure to move the gas to customers, however, in a deregulated market place customers may choose to purchase gas from a wide range of marketers, producers and brokers, the same way as is now done with home heating fuel. It is expected that several fuel companies will go after the kind of business opportunities that will open up with deregulation, which means that customers will have a choice to buy natural gas from a supplier other than the company that delivers it. The resulting competition among suppliers will translate into savings for the consumer.

Excretion of complement proteins and its activation marker C5b-9 in IgA nephropathy in relation to renal function

Directory of Open Access Journals (Sweden)

Onda Kisara

2011-11-01

Full Text Available Abstract Background Glomerular damage in IgA nephropathy (IgAN is mediated by complement activation via the alternative and lectin pathways. Therefore, we focused on molecules stabilizing and regulating the alternative pathway C3 convertase in urine which might be associated with IgAN pathogenesis. Methods Membrane attack complex (MAC, properdin (P, factor H (fH and Complement receptor type 1 (CR1 were quantified in urine samples from 71 patients with IgAN and 72 healthy controls. Glomerular deposition of C5, fH and P was assessed using an immunofluorescence technique and correlated with histological severity of IgAN and clinical parameters. Fibrotic changes and glomerular sclerosis were evaluated in renal biopsy specimens. Results Immunofluorescence studies revealed glomerular depositions of C5, fH and P in patients with IgAN. Urinary MAC, fH and P levels in IgAN patients were significantly higher than those in healthy controls (p Conclusions Complement activation occurs in the urinary space in IgAN and the measurement of levels of MAC and fH in the urine could be a useful indicator of renal injury in patients with IgAN.